Behavioural Neuro Lecture Notes PDF

Behavioral Neuroscience (red- need to know) Lecture 1: September 9 Mechanisms and Levels of Analysis -​ A mechanism is a description of a system's behavior built from a description of the actions and interactions of the systems parts (will be on test) What kinds of systems have behavior?...

Behavioral Neuroscience (red- need to know) Lecture 1: September 9 Mechanisms and Levels of Analysis -​ A mechanism is a description of a system's behavior built from a description of the actions and interactions of the systems parts (will be on test) What kinds of systems have behavior? How can we describe those behaviors? -​ Watches “behave” -​ Arms go around and around - that is a behavior -​ Other systems not just objects: Stock markets ​ Many people, bots, algorithms, are making purchases and sales orders ​ Parts of a system would include: stock brokers, consumers Mechanism of Mind? -​ We have to start smaller, more concrete -​ We need to choose a specific psychological phenomenon -​ Ex behavior: moths flying to light (simple?) -​ What are the “parts” of these systems? - Brain Cells, circuitous of brain cells, networks of circuits of brain cells -​ A sequence of events: ​ The first step is that they have to sense the light ​ The light is a signal coming from the environment ​ Information is a signal that acts on parts that then signal. Information changes the fact that there is light. Also where the light is, not just there is light. It comes from a certain direction, there is a sensor ​ There has to be a way of controlling movement in getting to the light - following of the wings ​ These are critical for certain mechanisms ​ The system makes something work in unison - a bunch of mechanisms together Sensorimotor behaviors, behaviors that involve emotion, behaviors based on reward value, behaviors based on long-term memories, social behaviors -​ All of theses behaviors require thinking about the system in two ways 1.​ As interactions between parts (brain cells) 2.​ As “transformations” of information -​ How do we connect “brian cells” with “information”? -​ How do we understand how brain cells work, and how they act/interact with one another? Summary: -​ Definition of mechanism: a description of a system's behavior built from a description of the actions and interactions of the systems parts -​ Actions and interactions of parts can also be thought of as integration of information -​ Mechanisms can be described across different levels of analysis Lecture 2: September 11 Nervous System Overview 1.​ Neuroanatomy basics -​ Terms to orient by -​ CNS -​ PNS -​ Organizing principles 2.​ Into to cells of the nervous system -​ Neurons and Glia What do we see under the surface of the cell? Cerebral cortex is a very thin layer, folded up in humans on the surface of the brain, a lot of the higher level functions go through cerebral cortex Front of the brain: frontal lobe, cerebral cortex. Planning, actions, setting mood depending on context Temporal lobe: cerebral cortex, emotional processes and hearing, who we interact with, who we see and hear. Nervous system directions: -​ Planes: ​ Coronal (vertical) - peacock fan (looking from the front or behind) ​ Sagittal (ear-ear) - mohawk (looking from the side) ​ Horizontal - Aerobie head (top or bottom) -​ Axes: ​ Anterior-posterior ​ Dorsal-ventral ​ Medial-lateral The nervous system is NOT ONLY THE BRAIN -​ In vertebrates (animals with backbones) -​ Central nervous system (brain and spinal cord) -​ Peripheral nervous system (nerves and autonomic nervous system) everything outside the CNS What is the Central Nervous System (CNS)? -​ Blood does not touch the cells of the CNS: the blood brain barrier (blood cells never touch your neurons) Barrier made up of glial cells that prevents blood from crossing but does let some molecules cross over -​ Oxygen and nutrients from the blood reach the CNS through the cerebral spinal fluid (carrier a lot of nutrients that the neurons are floating in) Womens runny nose turners out to be fluid leaking from her brain: leaking cerebrospinal fluid What are the parts of the brain?  -​ The cerebrum is the major part of the forebrain, also thalamus and hypothalamus (middle of the brain) hypothalamus important form hormones and cerebellum means little brain very important for motor control and moving -​ Brain stem - midbrain, medulla, pons -​ The parietal lobe is dorsal from the temporal lobe -​ The occipital lobe is posterior to the frontal lobe -​ Occipital: vision, visual system -​ Temporal: Meaning -​ Parietal: Spatial information (communicates closely with frontal lobe) -​ Fontal: how to move (how we move in relation to parietal lobe) What are the links between the CNS and the body? -​ Nerves: bundle of axons -​ Central nerves -​ Spinal nerves -​ Long stretched things of the nervous bundles together and they are all going to signal to an organ or muscle The Autonomic Nervous system -​ Primarily involved in regulating internal organs (heart, stomach, lungs) -​ Sympathetic nervous system: increases the body's use of energy, heart rates faster -​ Parasympathetic nervous system: activates the body's consumption and storage of energy, heart rates slower Not all species brains look the same, why?: Organizing principles of the nervous system -​ The nervous system is organized in a hierarchy of loops: sensation → action (“reflex arcs”). -​ Sensory system signals to the motor system then abc to the environmental system. Called a sensory motor loop or a reflex arc -​ Integrated sensory integration and then you get a very abstract environment and where everything is and where things are going. -​ Very abstract code/information that can buy us or control our signals. (motor circuit) -​ Sensory motor loops Summary of nervous system overview -​ organisms/individual animals -​ Planes: sagittal, coronal, horizontal -​ Aces: anterior-posterior, dorsal-ventral, medial-lateral -​ CNS: ​ Spinal cord ​ Brainstem ​ Cerebellum ​ Thalamus and hypothalamus ​ Cerebrum ​ Lobes of cerebral cortex (frontal, parietal, temporal, occipital -​ PNS: ​ Cranial nerves ​ Spinal nerves ​ Autonomic nervous system (sympathetic and parasympathetic divisions) Basics about Neurons -​ Soma: The cell body -​ Dendrites: branches from the cell body and receives signals from other neurons -​ Axon: branching extensions from cell body and transmit signals to other neurons -​ Axon Hillock: connection between soma and axon. Makes a decision -​ Nucleus: DNA is kept here -​ Signals come into the dendrites and they get integrated near the soma, at the axon hillock makes a decision and then it goes down the axon, and causes the nervous to speak to other cells through the axon terminals. When signals come into the dendrites they come in electrical. Glial Cells Astrocytes: -​ Interface between circulatory system and nervous system -​ Provide structural support -​ Can modulate local neuron activity (mess with astrocytes you mess with the whole system) -​ Make up the blood brain barrier, surrounded the blood vessels Oligodendrocytes and Schwann Cells: -​ Wrap axons with “myelin” (wrap) -​ Oligodendrocytes: many branches, found in CNS -​ Schwann: one branch, found in PNS -​ Tentacles come out and they wrap around the axons, important for electrical insulation and if you don't have the wrapping you can't get the signals through to the axons Microglia: -​ An essential part of the brain's immune system -​ “Macrophages” (engulf things around them and help develop nervous system) -​ Engulf molecules/foreign bodies that shouldn't be in the nervous system Key terms/concepts -​ Orienting ourselves: ​ planes: sagittal, coronal, horizontal ​ axes: anterior-posterior, dorsal-ventral, medial-lateral -​ Anatomy of the nervous system - Central Nervous System (CNS = brain & spinal cord) ​ cerebral spinal fluid, not blood (blood brain barrier) ​ Regions: -​ Cerebellum -​ Brainstem -​ Thalamus & hypothalamus -​ cerebrum (cortex: frontal, parietal, temporal, occipital) -​ Peripheral Nervous System (PNS): ​ Nerves ​ Autonomic nervous system (sympathetic and parasympathetic divisions) -​ Cells of the nervous system: ​ Neurons (parts: axon, axon hillock, dendrites, soma) ​ Glia (types: astrocytes, oligodendrocytes & schwann cells, microglia) Lecture 3: September 16 From Molecules to Cells -​ To understand mechanisms of behavior, need to understand actions and interactions of the nervous system parts: start with individual neurons -​ How do individual neurons act? ELECTRICITY History -​ Late 1700s: Galvani accidentally discovers the importance of electricity for biological movement -​ (this led Volta to create the first battery) Electricity -​ Parts of atoms have electrical charges: ​ Negative charge (-) ​ Positive charge (+) -​ Electricity is when these charges collect and move Building a Neuron that signals -​ Water (H2O) -​ Lipids (chains of carbon atoms (faith and oil)  -​ Proteins (chains of amino acids) -​ Ions (single atom that, when in water, have a positive r negative charge Water and Lipids -​ H2O: polar -​ Carbons: non-polar -​ They are Amphiphilic molecules: The tails are hydrophobic (water hating) and the heads (+) are hydrophilic (water loving) -​ Lipid bilayer -​ Cell membrane (plasma membrane). Lipid bilayer that forms neuronal membrane. The membrane is made up of the lipid bilayer. The cell membrane is made up of the amphiphilic molecules -​ Water and oil (lipids) don't mix because water is polar. Water is thermodynamically stable Proteins -​ Many proteins span the cell membrane Why? What function might this have? - transportation of molecules, to interface generally between the inside and the outside. It just needs to be there -​ Can put these amino acids together and can get different ‘shapes’ -​ Proteins are the machinery of the cell, made up of chains of amino acids. Ions -​ Most important ions for current: ​ Na+ (has lost an electron) ​ Cl- (has gained an extra electron) ​ K+ (has lost an electron) -​ NaCl (salt) → (H2O) → Na+ and Cl- -​ Do well in water, they don't do so well in oil because water is polar and oil just doesn't make sense thermodynamically -​ If there's no water around you get crystalized (salts) Summary of Important classes of molecules -​ Water: fluid inside (Cytosol - fluid inside cell) and outside of the cells (extracellular fluid)  -​ Amphiphilic molecules: (mostly fat). The membrane (skin) of cells separating incisive vs outside -​ Proteins: machinery and bridging the inside and outside of cells -​ Ions: electrical charge inside and outside cells with uneven distribution across the membrane (this creates an electrical potential). This creates a voltage (electrical potential) -​ Large molecules (mostly proteins) with negative charges anchored inside of cells -​ Pumps are secondary the channels are primary.Pumps require energy and are active and channels don't need energy the just open and close How do molecules interact with one-another in a neuron -​ Large negative molecules stuck inside of the cell (mostly proteins) -​ Ions Outside of cell cant pass through the membrane expect: some membrane proteins are ion channels only allowing K+ ions to pass through -​ K+ becomes concentrated inside of the cell to counteract the negative charge on larger molecules. -​ You never have single charges all by themself, you have them balanced. Potassium ions can travel through the membrane channel at their own will. There is a channel for sodium but it is closed off. -​ 2 potassium for ever sodium -​ K+ refers to the concentration of potassium: ​ High K+ inside but not outside the cell ​ Na+ is high outside the cell but not inside -​ Sometimes there is leakage. We start off with cells that have different ion concentrations inside and outside. This is due do: ​ Selective ion channels ​ Ion pumps -​ Because there are so many K+ ions inside the cells, and so few outside the cell, we get a voltage across the membrane -​ Voltage: the electrical potential (or push of electrons/ions) between two points -​ We call this membrane potential (requires an energy process) -​ Membrane potential and voltage are the same thing Membrane Potential -​ Negative membrane potential -​ Have potassium channels, more potassium inside the cell compared to outside the cell. Positive wants to leave the cell, which means it is a negative potential inside the cell. -​ The more an ion can move across the membrane, the more the membrane potential determines that ions concentration difference. (high potassium inside low outside, has the potential to move so you have an electrical potential) 1.​ How much do LARGE negatively charged proteins inside the cell influence the membrane potential? - cannot move across the membrane at all, they don't contribute directly because they are anchored they cannot move 2.​ How much do potassium ions influence the membrane potential? - contribute a lot because they can move freely 3.​ How much do sodium ions influence the membrane potential? - they cannot move across the membrane at all, the sodium cannot move. It does not contribute because it is at rest. -​ The more the ion can move across the membrane the more it contributes to the membrane Meme Version Relationship between ion concentration and membrane voltage Potassium inside the cell will make it negative. We want potassium inside and sodium outside -​ If the sodium channel was opened, sodium by itself inside the membrane will not give you a negative charge, unless there is an abnormality (not likely). The membrane also wants sodium out. -​ More positive ions can leave (there's a strong negative electrical potential) -​ More positive can enter (there's a positive electrical potential) -​ Once the sodium pumps open the cell becomes very positively charged (sodium becomes very excited and over powers the potassium ions) -​ At rest the Cl- channels do not contribute. Chloride has the potential to go into the cell but it is (-) charged. (in means negative and out means positive for chloride ions) Ion Channels -​ Ion channels can open and close depending on the factors affecting them -​ Some ion channels are ligand-gated: extracellular chemicals attach to the protein, causing the channel to open. If the gates are open you change the electrical environment. -​ Some ions channels are voltage dependent: changes in the membrane potential (from other channels opening/closing) cause the channel to open/close. Electrical change then you open up the channel. -​ Excitatory postsynaptic potential: a positive voltage charge (depolarization) caused by opening of ligand-gated ion channels (usually sodium channels) at a synapse. -​ Inhibitory postsynaptic potential: a negative charge caused by the opening of a ligand-gated channels (usually chloride channels) at a synapse Action Potential: rapid change in voltage caused by a positive feedback effect involving voltage-sensitive sodium channels -​ Depolarization: Goes up and up (EPSPs) when the sodium channels are opened then you hit a threshold and it shoots up to 0mV. Positive feedback loop once one sodium channel opens up the rest do and you get the spike that is called the action potential. Then it plumits, the sodium channels get blocked and they all closed -​ -70mV essential at rest -​ Hyperpolarization: overshoots to stop another action potential. The potassium channels are voltage gated. They start opening up and you get an overshoot. Voltage-sensitive calcium channels are located in high density at the axon hillock This is where the EPSPs and IPSPs are summed together (where synaptic integration takes place) Lecture 4 Review -​ Lipid bilayer made up of amphiphilic molecules (heads and tails). The tails are lipids and they are hydrophobic, heads are charged positive or negative and are hydrophilic. Proteins attached to the outside and inside the bilayer, are anchored in the inside of the membrane and have more negatively charged molecules than positive. This is a channel for atoms that lose charge when floating in water; the channels are open for potassium; you tend to have multiple potassium ions inside the cell counteracting the negatively charged ions. The fact that it is open is because the membrane is permeable to potassium, that permeability means something for us electricity. It is a key concept that if the membrane is permeable to potassium that means the electrical potential (voltage) you will get a negative voltage because of all the positive inside. Sodium ions have a lot outside the cell and few inside the cell, the membrane is not permeable to sodium. -​ What can we do to the neuron to make the voltage go positive?: we can open sodium channels, make it permeable to sodium. The voltage will become positive if the sodium channels are opened up. -​ The pumps are not a channel, they are hardworking and need energy to work. Channels just open up and don't take energy. Neuron Communication Permeability: -​ What does it mean? -​ Why is it useful? The sodium potassium pump is a protein that A) Moves sodium and potassium into the cell B) Moves sodium and potassium out of the cell C) Moves sodium into the cell, and potassium out of the cell D) Moves potassium into the cell, and sodium out of the cell Ions permeability through the membrane is important -​ How can we change it?: ​ Ligand gated: channels attach = open channel -​ They tend to be in the dentrids and stoma, so when you have chemicals/input coming in they will act on ligand gated ion channels and it will cause EPSPs (excitatory postsynaptic potential). These will collect and combine together and when they do they will cause the voltage gated sodium channels to change and open up (at axon hillock) ​ Voltage dependent: membrane potential change = open/close channel -​ When you've already started to change the membrane potential that can cause a positive feedback loop (if one thing happens it causes more of the same to happen) once the voltage starts to go up it starters to depolarize once it starts this it becomes VERY depolarized this is call the action potential (big spike in graph) Excitatory postsynaptic potential (EPSP): -​ a positive voltage change (depolarization) -​ caused by the opening of ligand-gated ion channels -​ usually sodium (Na+) channels Inhibitory postsynaptic potential (IPSP): -​ a negative voltage change -​ caused by the opening of a ligand-gated ion channels -​ usually chloride (Cl-) channels Action potential -​ Decisions happens at axon hillock (to signal to the next neurons)  -​ Rapid change in voltage caused by voltage gated sodium channels -​ Voltage sodium channels open and then caused massive depolarization that leads to the action potential -​ Positive feedback loop involving the voltage sensitive sodium channels. Voltage gated potassium channels cause the cell to become hyperpolarized (at the end of the graph) -​ Synaptic integration: depolarize events combine to either reach threshold or not (start) -​ Absolute refractory period: sodium channels are inactivated (middle). They become active soon after. -​ Relative refractory period: hyperpolarization by open potassium channels reduced likelihood of another action potential (end). -​ Why is it -55mV that it hits action potential right away? Voltage gated sodium channels start the action potential at -55mV they start to open up at -55mV. When it is no longer permeable to sodium it will shoot back down and hyperpolarize Many voltage sensitive sodium channels are in the axon hillock. This is where EPSPs and IPSPs are “added up” (synaptic integration) Presynaptic: release the chemicals Postsynaptic: receives this and opens up channels causing EPSPs Neuron signaling from synapse to synapse 1.​ Neurotransmitters evoke a response: neurotransmitters are a chemical released by a presynaptic neuron that acts on a postsynaptic cell ​ Receptor is something that is able to receive the neurotransmitters; ligand gated ion channels is a neurotransmitter receptor. One type of response is an EPSP. ​ If the ligand channel opens up the sodium channels it increases the permeability for sodium and it will depolarize 2.​ The electrical signals (EPSPs) travel through the dendrite, adding together. Dendrites receive inputs, axon hillock is the integration of EPSPs ​ You have many receptors, not just one. You have many synapses, that means you are potentially getting EPSPs across many parts of the dendrites; this means there is some kind of integration happening. ​ If you have the EPSPs at the same time they will travel through the cell, if you have 3 it will be twice as big compared to if you have 1. The electricity flows, the electrical change is traveling through the fluid (cytosol), movement of charge through cytosol very easily. The more EPSPs the more depolarized  ​ Synaptic integration: EPSPs you are adding and IPSPs you are subtracting. Synaptic integration happens because you have EPSPs along the dendrites. They are inputs from may different places that cause the action potential 3.​ Eventually the combined signal reaches the axon hillock and is depolarized (EPSPs and IPSPs) exceed threshold = action potential. ​ What determines how much depolarization is needed for an action potential?: voltage-gated sodium channels ​ Synaptic integration processes you get the adding of EPSPs through the dendrites. All the electrical current flows into the stoma and to the axon hillock, the axon hillock makes the decision with the voltage gated/sensitive channels, they make the decision to send the single out. ​ When the voltage gated channels open up at the axon hillock it causes an action potential 4.​ The action potential travels down the axon (through all branches). The action potential is repeatedly regenerated by voltage gated sodium channels in the axon. Itis actively propagated down the axon ​ Axon hillock filled with voltage gated sodium channels and this causes an action potential ​ Propagated: Voltage gated ion channels (green), the arrows depict that sodium can flow into the cell. They flow in and you get this local depolarization, this causes current to flow through the axon (red arrows). The current is going to flow through the cytosol, and over time it leaks away.. It wears off, the current change will only go so far if it wears off. ​ If the charge wears off, we have added generators that renew the action potential, which means there are more voltage gated sodium channels in the axon hillock. The current flows through the axon and the current gets recharged by the new channels. 5.​ The action potential reaches axon terminals, where there are voltage sensitive calcium channels ​ Calcium is very important. There are many proteins that are sensitive to calcium. It is important at the end of the axon. It i also important in the postsynaptic side of the neuron ​ The vesicles are little departments and it is made up of almost the same stuff as a cell membrane. They are filled with a chemical ​ Voltage gated calcium channels, they open up and allow calcium ions in, and many proteins are sensitive to calcium.  ​ The voltage is going to come down to the axon terminal and the action potential is going to hit the end. The calcium ions enter the cell and wreak havoc, if you have too many calcium ions it will die, you will have toxicity (program cell death) ​ When that happens it breaks down, calcium enters because voltage has changed, it causes scaffolding to break down and the vesicle fuses with the cell membrane and now they are part of the bigger collective 6.​ Calcium enters and interacts with proteins holding up membrane bubbles (vesicles) filled with neurotransmitters. The vesicles then collapse into the membrane. Neurotransmitter is released Myelin: is a lipid covering from glial cells that prevents voltage from “leaking” through the membrane, increasing resistance of membrane. They insulate. -​ Created by glial cells, schwann cells Nodes of Ranvier: small gaps in the insulating myelin sheath -​ There are breaks in the myelin and these spots are dense so you can renew the action potential, they are gaps in the myelin. -​ Have voltage gated sodium channels Voltage: sensitive sodium channels at the Nodes of Ranvier renew the action potential -​ With the myelin you are insulated so you don't wear out as fast but you still need to have the extra voltage gated sodium channels to renew the energy  -​ You have myelinated axons and the current is able to go very quickly -​ The more myelin you have the faster it will go because it takes less time to renew the energy. The action potential is much faster. You don't have to renew as often if you have myelin so you don't slow it down as much (Ex: changing tires in F1) Recap -​ EPSPs & IPSPs happen when ligand gated ion channels are open in the dendrites and soma -​ EPSPs flow through dendrites, adding together, if depolarization at the axon hillock reaches a threshold, then voltage-gated sodium channels open -​ The opening of voltage-gated sodium channels results in a massive depolarization: the action potential -​ The action potential flows down the axon, renewed by more voltage gated sodium channels at the Nodes of Ranvier -​ At axon terminals, there are voltage gated calcium channels. When the action potential reaches terminals, these open. -​ Calcium enters the axon terminal and reacts with proteins holding-up the vesicles. This causes vesicles to fuse with the membrane, releasing neurotransmitters into the synapse Lecture 5: Neuron Circuits Dendrites: receive inputs (EPSPs, IPSPs) Axon Hillock: integration of EPSPs (generates action potential) Axon: condition of action potential (“saltatory” conduction) Axon Terminals: outputs (action potential converted to chemical signal) Different Types of Neuron Signals -​ How would a neurotransmitter take a neuron closer to threshold for an action potential? -​ How would a neurotransmitter take a neuron farther from threshold for an action potential? Type of Signals part 1: Excitatory vs. Inhibitory -​ Excitatory: take a neuron closer to the threshold for action potential -​ Inhibitory: take a neuron farther from threshold for action potential -​ Whether a signal is inhibitory or excitatory depends on only ONE factor: what does the postsynaptic receptor do? Types of Signals pt. 2 -​ Direct vs. Indirect -​ Direct: neurotransmitters receptors are “ionotropic” (ligand-gated ion channels)  -​ Indirect: neurotransmitters receptors are “metabotropic” (G-protein coupled receptors) -​ Neurotransmitter binds to a protein on one side of the membrane, causing a chemical signal on the other side Types of Signals pt. 3 -​ Different chemicals, different neurotransmitters -​ Most prevalent neurotransmitter in the brain: ​ Glutamate - Excitatory ​ GABA - inhibitory (chloride channels) -​ Other common neurotransmitters (“neuromodulators”) ​ Acetylcholine ​ Dopamine ​ Norepinephrine ​ Serotonin Glutamate -​ An amino acid -​ The most excitatory neurotransmitter in vertebrates -​ Does not cross the blood-brain barrier (you can eat it, but don't put MSG directly on your brain) -​ MSG = monosodium glutamate (salt and glutamate) GABA -​ “Gamma-aminobutyric acid” (made from glutamate) -​ Primary inhibitory neurotransmitter in the brain -​ Chloride channels Neuron Circuits -​ Groups of connected neurons -​ Several types of neurons: ​ Excitatory vs. inhibitory neurons ​ Projection neurons vs. interneurons ​ Neurons with feed-forward and feed-back connections Excitatory vs. Inhibitory Neurons -​ The effect of a presynaptic neuron on a postsynaptic neuron depends on the receptor -​ Glutamate receptors are almost ALL excitatory - neurons that release glutamate = excitatory neurons -​ GABA receptors are ALL inhibitory - neurons that release GABA = inhibitory neurons Projection Neurons vs. Interneurons -​ Projection neurons: neurons with axons that go to other regions -​ Interneurons: neurons with axons that stay nearby Feed-forawrd and Feedback -​ Feed-forward connection: a neurons synapses onto a second neuron (A → B) -​ Feedback connection: a neuron synapses back onto a neuron that signaled to it (A ↔ B) How do we measure how a circuit is “behaving”? What is the output of a neural circuit? -​ Firing Rate: number of action potentials over a period of time  ​ Strong stimulus causes more action potentials and weak stimulus cause less Neuron Circuits Examples -​ Ex 1: The Stretch Reflex - inhibitory neurons coordinate opposing processes Ex 2: The Oscillating Circuit -​ Inhibitory neurons help generate oscillations, capable of pacing information flow Ex 3: Lateral Inhibition -​ Inhibitory neurons can increase the contrast between similar (spatially adjacent) inputs -​ Feed-forward circuit -​ Row of neurons and they all have axon hillocks pointing the same way and they are pointing to another row of neurons. Say you poke the sensory receptor and it becomes very active (action potentials) should cause the other neuron to have an action potential. You don't know where the poke is from because both neurons are causing action potentials. To know where the poke is you add in inhibitory interneurons, these are projecting and are branching out to the side, they project to the side, theta are going laterally, they are kind of numbing the edges, sending signals off to the side to inhibit them and this increases the spatial contrast Lecture 6: Neuromodulation and Drugs Practice Q 1.​ You can take a neuron farther away from action potential by opening potassium (K+) channels, or by opening chloride (Cl-) channels. Why do both ions have a similar effect on the membrane potential? - makes cell negative and hyperpolarizes it 2.​ Why is it important that different neurons use different types of neurotransmitters in the stretch reflex circuit? - different neurotransmitters in the stretch reflex circuit allow for the coordinated excitation and inhibition of muscles, ensuring smooth, functional movements and preventing conflicting muscle actions In Westworld (HBO series) S3E5, Caleb is given a drug, Genre, that makes him experience a sequence of 5 different reality “modes”. In the neuron circuits, “modes” of neural interaction can be changed by the chemical environment. Neuromodulators set the mode for how it works. -​ Neuomodulatros: When you add a chemical to a no chemical it will change very quick and how the circuit is operating (the mode of the circuit) A neuromodulator can change the behavior of neurons within a circuit, and thereby change how neuron circuits behave -​ neuromodulators , molecules such as neurotransmitters and hormones, usually have slower and more global effects than the excitatory and inhibitory connections of a circuit -​ Metabotropic protein (G-protein) these are slower and more indirect. Neuromodulators are acting on these metabotropic proteins -​ Tend to move more slowly on a circuit, act ore globally they will signal to many different cells, they tend to have nuclei and they tend to be found in the midbrain (brainstem) and spread their axons in many places Neuromodulator neurotransmitters often come from specific nuclei in the brain, with axons that spread all over. They will release into other places in the brain. Let's look into detail at the classical neurotransmitter neuromodulators and drugs that affect them -​ Endogenous: “from within”, naturally occurring within the body (dopamine) -​ Exogenous: “from outside” introduced from outside of the body (drugs) (caffeine) -​ Agonist: a substance that activates a protein receptor, increases activity of protein -​ Antagonis: a substance that inactivates or competes for a protein receptor Acetylcholine -​ Effects on neurons: receptors are ionotropic and metabotropic -​ Ionotropic receptors are nicotinic (nicotine activates nicotinic receptor) -​ Metabotropic receptors are muscarinic What does acetylcholine do for behavior/cognition? -​ In the body: causes muscles to contract because acetylcholine is released by motor neurons, parasympathetic signaling -​ In the brain: attention and learning ​ More acetylcholine is typically found when you are paying more attention to things in the world around you -​ HOW?: maybe by increasing “feed-forward” signaling and decreasing “feed-back” signaling ​ Your acetylcholine ramps up and you're more in tune to the inputs in your brain, but if you don't have any acetylcholine might be low and your circuits in your cortex might be much more related to a feedback signal (internal thoughts) ​ Low acetylcholine is not paying attention and you might be listening or thinking about internal thoughts (memories, what you're gonna eat later) ​ High acetylcholine means you are paying very close attention and very engaged Dopamine -​ Effect on neurons: ​ Metabotropic receptors: D1 receptors are excitatory (close up potassium channels) and D2 receptors are inhibitory -​ Dopamine is both inhibitory and excitatory it depends on the receptor the cell has ​ Nuclei with dopamine neurons: substantia nigra and ventral tegmental area (VTA) ​ Dopamine increases when you want things (motivation) What does Dopamine do for behavior? -​ Motivation -​ Skill learning -​ Value learning Dopamine: Cocaine -​ Drugs that increase dopamine tend to be pleasurable but addictive -​ Cocaine: made up from coca leaves (add chemicals to the leaves then becomes cocaine) -​ Can cause euphoria, high energy, and extreme confidence  -​ Can (eventually) cause anxiety, paranoia, and motor changes -​ Cocaine increases dopamine synapses by inhibiting neurotransmitter reuptake pumps (axon terminal). ​ Neurotransmitters reuptake pumps, they are folding in and out. They are picking up the neurotransmitters and bringing them into the terminal. Dopamine: Amphetamine -​ Can increase energy and attention, elicit feelings of pleasure -​ Very similar mechanism to cocaine Norepinephrine (noradrenaline) -​ Effect on neurons: metabotropic receptors (“alpha” and “beta”) -​ Norepinephrine neurons are found in the locus coeruleus -​ Beta blockers are used to control anxiety (don't cross the blood brain barrier) it is reducing sympathetic nervous system activity -​ Sympathetic nervous system uses norepinephrine as their signal What does norepinephrine do for behavior/cognition? -​ In the body: signaling in the sympathetic nervous system -​ In the brain: increases wakefulness, motivation, learning and attention Norepinephrine: Adrenergic Drugs -​ Cocaine and amphetamines (like dopamine) -​ Dopamine and norepinephrine are both catecholamines -​ Beta Blockers can inhibit stress responses (body) Serotonin (5-HT) -​ Effects on neurons: MANY different receptors. Almost all are metabotropic -​ Serotonin neurons are found in the rape nuclei (close to the spinal cord, brain stem) What does Serotonin do for Behavior? -​ Influences motivation, mood, “waiting” -​ HOW?: complicated, different across many circuits -​ Fun fact: higher tryptophan in the diet = more serotonin bananas, dates, milk, chocolate, sesame seeds -​ What it does for behavior really depends on the circuit you are looking at. Serotonin can increase or decrease anxiety Serotonin: Drugs -​ “Selective serotonin reuptake inhibitors” (SSRIs)  -​ MDMA (“ecstasy”) -​ Psychedelics: psilocybin (from mushrooms), DMT (from ayahuasca and other plants), mescaline (from peyote cactus), LSD (“acid”) Serotonin: Serotonin reuptake pumps -​ SSRIs: often used to treat depression, anxiety -​ Inhibit serotonin reuptake pumps -​ The neurotransmitter reuptake pumps, they go in and out and open up Serotonin: MDMA -​ Increases serotonin in the synapse but also decrease the amount of serotonin that is being taken up to the presynaptic terminals -​ Induces feelings of increased energy, euphoria, emotional warmth, perceptual distortions -​ The days after people take molly sometimes there is a crash where they feel very depressed and low energy (changes in serotonin in release, adaptation of the drug acting) Serotonin: Psychedelics -​ Psilocybin (from “shrooms”), mescaline (from peyote cactus), DMT (from ayahuasca & other plants), and LSD (“acid”, from a fungus) all act on serotonin receptors -​ How do they cause altered perceptions, disordered thinking, and hallucinations? ​ Some shift, top down vs bottom up activity Caffeine -​ Inhibits receptors for adenosine -​ Adenosine may build-up over periods of waking and cause you to become sleepy (by decreasing other neuromodulators). Caffeine inhibits these receptors and prevents us from becoming sleepy -​ Different from classical neurotransmitters: adenosine accumulates over time, not released in vesicles into synapse -​ Antagonist - Inactivates Agonist - activates protein Opioids -​ A type of protein (“neuropeptide”) - protein that is packaged into vesicles but the vesicles are different, they are clear vesicles. Dense core vesicles makes you know there is a neurotransmitter in there -​ Endogenous opioids = endorphins -​ Can decrease pain and increase pleasure -​ Ex of exogenous (putting into body) opioids: morphine, heroin, codeine, oxycodone, fentanyl -​ Different from classical neurotransmitters: large molecules in large “dense core” vesicles  -​ Important for pain pathways, opioids are released to inhibit pain Cannabinoids -​ Endogenous cannabinoids = Endocannabinoids -​ Exogenous: come from the cannabis plant ​ Stimulate appetite, influence attention and working memory ​ Different effects in different individuals (relieve anxiety vs. cause anxiety -​ Many different cannabinoids (CBD, THC) -​ Cannabinoid receptors are metabotropic -​ Cannabinoid receptors in the brain (CB1 receptors) are found on the axon terminals of certain neurons -​ Different from classical neurotransmitters: released by the postsynaptic cell and act as a retrograde (back) signal Lecture 7: Neurons and Circuits of the Eye Practice question: Which of the following is most likely to increase the amount of neurotransmitter in the synaptic cleft?? A.​ opening postsynaptic calcium (Ca2+) channels B.​ opening presynaptic potassium (K+) channels C.​ activating cannabinoid receptors D.​ inhibiting reuptake pumps Basic Principles of Sensory Systems -​ Sensation: transforming physical stimuli (light, energy, mechanical energy, environmental chemicals) into signaling within the body (through neuron communication). Taste, hearing, smell. Your body is sensing what is going on around you -​ Perception: the acquisition of knowledge through sensation. Putting together the signals into something meaningful, something you can act on - this happened through sensory transduction How Does Sensation Happen? -​ Sensory Transduction: the process by which energy in the environment is converted into cellular signaling (sensation) -​ Sensory Receptor: a cell that performs a sensory transduction (not protein receptor). The receptor is a cell type. What Does The Visual System Sense? -​ Photons: units (or waves) of energy  ​ Released when something expels energy ​ More energy = higher wave frequency - gamma rays ​ Always travel at the same speed What do we use to sense light? -​ The EYE -​ You are actually flipping the image in your eye (light from the top goes to the bottom and vice versa). The brain then flips the image itself to make it right. We sense the world upside down and the brain flips it Essential Parts of the Eye -​ Pupil: space within the iris that allows light to pass through the lens -​ Lens: focuses light -​ Vitreous humor: fluid inside of the eye -​ Retina: 3 layers of photoreceptors and neurons lining the inner wall of the eye ​ Opsin is a light receptor -​ Optic nerve: bundle of axons carrying signals from the eye to the brain - ganglion cells The optic disc (blind spot) is where the axons of the retinal ganglion cells all converge to become the optic nerve The Retina: -​ Fovea: dense area of photoreceptors at the center of vision (in line with pupil). Things branch out from fovea. High density of cones and rods -​ Optic Disc (blind spot): area above the optic nerve where there are no photoreceptors -​ 3 Layers of cells: 1.​ Photoreceptors: ​ Rods: not color sensitive, but more sensitive to light ​ Cones: color sensitive, dense at fovea - different cones for different colors 2.​ Bipolar: “relay” to ganglion neurons - send to ganglion cells 3.​ Ganglion cells: axons go to the brain -​ How signaling happens through the retina, the cones and rods are connected with bipolar cells. The cones make up the color spectrum, the rods are more light sensitive.  These are the photoreceptors. The bipolar cells will signal to the ganglion neurons (send axons out of eye to the brain). Once you hit the photoreceptors, they change when stimulated by light - they open potassium channels, it will become more negative. Opening more potassium channels then are at rest will further polarize the neuron. We are causing them to release less neurotransmitters. Some are excitatory or inhibitory. -​ Inhibitory interneurons - one is near the photoreceptors (horizontal neurons) and one is near the ganglion neurons (Amacrine neurons) - these will slow down the energy, release GABA, and turn off other cells. Horizontal/Lateral stretch -​ What kind of information does a blue cone signal?: seeing a blue object, the light will bounce off of that and the blue will end up at the blue cone, blue cone with change its activity in response to the blue light/object -​ Open sodium channels you will depolarize -​ Dark Current: More photoreceptors if you close your eyes in a dark room. They release more glutamine than they normally release. Photoreceptors in the darkness have more depolarization because the release of more glutamate Opsin in humans are metabotropic (light receptor) - light opens potassium channels Human Vision is Trichromatic -​ All colors we see are due to combinations of three types of cones Firing Rate: number of action potentials over a period of time -​ The weaker the stimulus the less action potentials and the stronger the stimulus the more the action potentials (TEST) Baseline firing rate increase light increase the light = more active What information is this ganglion neuron signaling? -​ Send axons into the brain from the eye -​ Signaling “is there light in a certain area of the visual field?” Between photoreceptors and ganglion neurons in the 3 layers of the eye there is horizontal neurons (inhibitory interneurons) Bigger the light = more action Outside the circle = less action potential Lateral Inhibition -​ Strength of sensory input over space -​ Relative neuron firing output across space (the Hermann Grid Illusion) -​ Center-surround firing is probably caused by lateral inhibition Different types of cells are specialized for different functions -​ Each of 10-20 types of ganglion cells carries different types of information to the brain ​ Color, light at large and small spatial scales,movement (any direction), texture, approaching movement, anticipated position -​ Each ganglion cell can be thought of as the output of a circuit -​ Each circuit computes different information -​ Amacrine neurons: many different kinds, many different neuron morphologies. Leads to the ganglion neurons to signal different information  Region to region signaling, as well as parallel signaling that gives you many different types of information What have we learned about the brain from just looking at the retina? 1.​ Information processing is both serial and parallel - serial is happening in a line or a sequence and parallel processing is happening all at once, many at one time 2.​ Information processing involves the actions and interactions of circuits with both excitatory and inhibitory neurons 3.​ There is information about where in space things are happening (there are maps of external space) as well as information about what is in that space Midterm 1 Review -​ (50 MC questions full class time) -​ Lectures 1-6 -​ On computer -​ Membrane potential questions -​ 0 permeability: what is your membrane potential ? = 0 as soon as you start having permeability you start to have membrane potential -​ Some diagrams Lecture 1 -​ What is a mechanism: description of a system's behavior, based on how the parts act and interact with each other. Take a system and separate into parts and how do those individual parts act and interact -​ The levels of analysis Lecture 2 -​ Overview of the Nervous system  -​ Planes (coronal, horizontal, sagittal, dorsal…) basic sense of where things are in the brain (frontal, occipital, parietal, temporal) -​ Parietal cortex is dorsal to the temporal lobe -​ Blood brain barrier- protects the brain from toxins and nutrients from getting into the brain, prevents the blood from touching neurons. Barrier between blood and neurons. Made up of glial cells. -​ oligodendrocytes/schwann cells: make up the myelin (insulation around the axon) -​ Microglias: removal, waste removal -​ PNS - everything but spinal cord and brain, muscles, organs. Autonomic nervous system = parasympathetic and sympathetic nervous system -​ CNS - spinal cord and brain Lecture 3 -​ From molecules to neuron -​ Amphiphilic molecules that make up lipid bilayer, ions both inside and outside (potassium inside and sodium outside) Potassium can get in at rest sodium cant and thai translates to a membrane potential (voltage), some sodium ions can get in and the sodium potassium pumps push it out and compensate by brining potassium back in -​ Protein channels ​ Ligand gated ion channels = ionotropic receptors, open and can cause EPSPs and IPSPs ​ Voltage gated ion channels = action potentials ​ Metabotropic receptors = not channels, in the membrane, they can change when a chemical is present extracellularly and that will change chemicals inside the cell ​ Chloride channel are responsible for the IPSPs Lecture 4 -​ NMDA receptors = detect chemicals/glutamate/ligand but is also voltage gated, so need both to open -​ Neuron -​ Action potentials (depolarize, hyperpolarize, threshold) -​ EPSPs and IPSPs -​ Why is it inhibitory - depends on receptors and where (GABA every receptor is inhibitory) -​ Retrograde signal - backwards, feedback -​ Synaptic integration: the neuron is constantly integrating. They are doing this but only if they reach the -55mV to start an action potential. Voltage gated sodium channels they open up because we got to -55mV and then you get up to 40mV but them shoots back down because the sodium channels close, and the potassium floods in, the sodium channels are inactivated (this is called the absolute refractory period)  -​ reflective refractory period = hyperpolarization - more potassium channels are open than usual Lecture 5 -​ Circuits -​ In the brain what we call circuits it's mostly the excitatory neurons talking to each other (glutamate) and the inhibitory (GABA) -​ Feedforward connections or feed back connections -​ Neurotransmitters -​ Spinal feed forward inhibition - bicep and something pushes on the hand that is detected by stretch receptors by the bicep and it will go into the spinal cord, it will synapse onto a motor neuron and goes back out and stimulates the muscle and it will depolarize and contract (body detects the stretch) - also synapses onto a inhibitory interneuron, you contract one muscle but release the opposing muscle - you can have one signal to go back and contract your muscles but you also have another signal saying release that opposing muscle -​ Feedback inhibition - give rise to oscillations -​ Lateral inhibition - feedforward Lecture 6 -​ Neuromodulataors, most act on metabotropic receptors -​ Drugs -​ Norepinephrine - adrenergic receptors = adrenaline receptors -​ Opioids - neuropeptides = bigger and kept in large dense core vesicles Lecture 8: Vision in the Brain Retina -​ Information processing is both serial and parallel -​ Information processing involves the actions and interactions of circuits with both excitatory and inhibitory neurons -​ There is information about where in space things are happening (i.e., there are maps of external space) as well as information about what is in that space -​ Light hits the retina and the eye has the 3 layers, and they have the retina ganglion neurons - sometimes they have activity where you don't see any or only a few action potentials (firing rate can increase by the light hitting one particular part and you will get change of signaling to bipolar  cells, which then changes activity in the retina ganglion neuron which then causes changes in action potentials) -​ Cones = color receptors (red, green, blue) -​ Sometimes there was a period of inhibition, before or after the red ball passed the visual field; these are called center surround visual fields. Some periods of time you have zero action potentials because those are inhibitory interneurons (lateral inhibition). -​ Retinal ganglion cell axons = the optic nerve (sometimes in the optic chiasm) -​ Half of the axons cross the optic chiasm → lateral geniculate nucleus of the thalamus -​ neurons in the lateral geniculate nucleus have axons that = primary visual cortex (V1) ​ Goes from the retinal ganglion axons to optic nerve to optic chiasm to the thalamus (lateral geniculate nucleus) then to the back of the brain in the primary visual cortex (V1) ​ As the axons get to the thalamus some of them cross over to the other side of the brain, the neurons on the left part of the left eye seem to stay on the same pathway on that side of the brain but then the other side the right side of the left eye crosses over. Left visual information hits the right side and then the right visual information hits the left side of the brain. (right goes to left, left goes to right) ​ Why would you want information to cross over? - if you have information from the left and hits the right side of your body (contracts muscles) it takes you away from the stimulus you just got information from. Contracting reflexes Blindsight: patients with damage to primary visual cortex (cortical blindness) can still make visual judgments, but are not conscious of the visual stimuli -​ You can’t have blindsight without a thalamus Overview of the Neocortex -​ A folded sheet about 2.7 square feet, 2-4mm of 6 layer neurons. Layers are connected in organized ways -​ “New bark” lots of layers -​ Vision gets processed usually in the 4th layer -​ In the primary visual cortex, and is a retinotopic map. The retina and the primary visual cortex match each other by having a retinotopic map The primary visual cortex: Layers vs. Areas -​ Serial processing happens between layers (and between brain regions) one after another ​ Sequence = serial  -​ Parallel processing happens within a brain region, across small areas (columns) of cortex. Small area of cortex, all those neurons tend to be connected with each other and this is a column of cortex (like a circuit) Types of information found in primary visual cortex: -​ Where: ​ Visual space - V1 is organized with a map of the retina, depth perception ​ How far away - neurons get more or less input from right vs. left eyes (interweaving left and right eye strips) -​ What: ​ Shape = the direction of lines/edges - many neurons in V1 are selective for lines/edges of certain orientations ​ Shape = the thickness of edges - neurons are also selective for certain thicknesses ​ Color - “blobs” are color selective neurons “interblobs” non-color selective (more spatial information) Retinotopic Map -​ V1 Has a map of the retina -​ Neurons closer together in V1 are more likely to… -​ The map is distorted -​ There is more space devoted to the fovea (why is this not surprising - think cause and consequences) ​ Consequences (function): What you want to process, you look at that area because you want that information. Maximizing resources dedicated to what you care about. Get more further processing, you get to be more aware of that part of your visual field ​ Cause: The fovea is dense with many cones, more photoreceptors there is more density you end up getting a lot of neurons dedicated for the fovea. More photoreceptors in that part of retina (fovea) more cells will signal to more cells in the cortex and you'll have more area dedicated to the fovea -​ V1 is organized with a map of the retina (neurons closer together in V1 are more likely to have more visual space that are responding to) , depth perception Hubel and Wiesel -​ Action potentials on different lines (horizontal, vertical, diagonal…) - does not fire on horizontal lines, the most firing is in the vertical line How orientation cells may arise from center surround cells -​ Neurons with center surround fields corresponding with different parts of the retina  -​ All go through the optic nerve (also nervous in thalamus are getting this input and signaling to the cortex) The cortex is layered (usually to layer 4 of V1) -​ Some is getting input from right eye and some from the left eye -​ Map the visual field to retina - the neurons have to have their axon not only going to different places but converging to the same postsynaptic neuron -​ Certain neurons fire more action potentials when light hits them (responsible for different friends of light) Visual cortex computes high - and low - frequency features -​ Combine into something meaningful -​ Your data from the eye/thalamus is basically a chopped up photo that's pixelated. Low spatial frequency would be blurry and high would look like a black and white sketch (edges) and adding these together make a meaningful stimulus After V1 - Information processing is divided into two streams/pathways 1.​ “Where”: location & movement of visual input, relative to eye, head, body, or the rest of the environment, more dorsal 2.​ “What”: combining visual features into objects and meaning more ventral (what is this? What are they associated with?). Has top down and bottom up The “What” Pathway -​ “Bottom-up” We put features together into greater wholes (e.g., “center surrounds” into lines) ​ Keep going up and up, from start to finish -​ “Top-down” We also use memory, expectations to put features together ​ Arrows that feedback into early regions ​ If we don't know what something is we want to signal back and this can be helpful for memory, fill in the blank, and also direct the processing and which features are emphasis according to what is important ​ Immediate memory of what you're looking at  -​ “What” pathway: in the temporal lobe, some neurons will fire for specific objects or specific people ​ A Steve Carell cell - 3 different photos of Steve Carell and we know enough infraction about that to fire and be like I know who that is in all 3 photos Fusiform Face Area (FFA) -​ Faces are processed “holistically” -​ Prosopagnosia: inability to recognize faces -​ Fusiform face area isn't always JUST about faces - 10 of the same dog in a line can you recognize all of them as their names based on their facial features (can train yourself to do this) Damage = barely able to recognize people can only recognize certain faces “Where” (doral) Pathway: Place and Movement -​ Area V5/MT - in occipital lobe -​ Akinetopsia: patient LM ​ Difficulty crossing the street, pouring fluids ​ Damage to this area no longer able to see movement (can't cross street cause they can't figure out how fast or slow the cars are going) Where and what information can also depend on one another -​ Features we group together as objects depends on how we look at space -​ Depend on each other -​ Once you know the where you can see the what Lecture 9: Touch and Sound Nobel Prize for medicine 2021: Somatosensation -​ David Julius -​ Ardem Parapoutian Transduction of Light: photons → opsins → polarized rods/cones → less neurotransmitter onto bipolar cell -​ Touch and Sound: Matter → pushes against other matter ​ Atoms cant pass through each other) - matter has inertia - if you push on one part, it is going to take some force to yield to that pressure -​ Mechanoreceptor: cells that detect matter pushing against other matter ​ How? → often, ion channels are pushed open = mechanical stimulation Touch - Somatosensation  -​ Multiple types of mechanoreceptors found in the skin -​ Pascinian corpuscle: deep in skin large (look like small onion)- vibration/sudden touch -​ Meissner’s corpuscle: Medium-sized- movement across skin -​ Merkel’s discs: Small, Near surface of skin- static touch -​ Ruffini endings: Relatively deeper in skin- skin stretch -​ Also: open nerve endings (Not mechanoreceptors, but important for temperature, pain, etc.) Mechanoreceptors differ in: -​ Spatial scale - size of receptive fields ​ Leaf vs tree vs frost -​ Temporal scale - speed and respond and adapt ​ A strawberry turning from yellow to red ​ Rapid adapting: first putting on a jacket, feeling the weight of it. However, the stimulation wears off Somatosensory Anatomy 1.​ Axons cross to the other side of the brain (“touch: axons cross at different level from “pain”) Spinal cord 2.​ Brainstem 3.​ Thalamus - sends the signal to the cortex, located in parietal lobe 4.​ Cortex - Primary Somatosensory Cortex Central sulcus: everything in front is frontal and is concerned with actions, careful planning. Everything behind tends to be more involved in tracking perceptual things Primary Somatosensory Cortex: Postcentral Cortex -​ Located in the anterior part of the parietal lobe, where it constitutes the postcentral gyrus -​ General sensations of touch, pressure, pain, temperature, and proprioception Organization of neural codes in the somatosensory cortex: homunculus -​ Each body part sends information to a specific part of this strip. This creates a topographical map of the body in the cortex (homunculus) -​ Homunculus: brain map of your body, in the sensory strip of the cortex, where sensory input like heat of pain is received. Different parts of your body have more or less receptors for sensation From the primary somatosensory cortex information flows to… -​ Formal motor cortical areas -​ “What” (ventral) and “where” (dorsal) processing streams -​ Reward areas Temperature -​ TRP receptors in the skin sense temperature Top-down Control over Pain -​ In the visual brain, you can see there is bottom-up, putting features together (frequencies of spatial edges), which is also in primary somatosensory, you put together the features (feel a grab on the arm, many features that can put it together in a bottom up way) -​ Why might we want top down in the somatosensory cortex? - the situation, memory, cortex “learns” if you have felt something in the past, it influences your choice to touch it again (phantom limb syndrome) -​ The situation, what might be touching you? Ex: a fine touch on your shoulder, but you are in the jungle, you will freeze and brush t off (scared), but if you are in your own home, that might be a good thing, you might not swat it off -​ The anterior cingulate cortex: received signals about pain and reward -​ Also can signal opioid release in the brainstem and spinal cord → inhibiting pain signals -​ “Mind over body” Audition - hearing Sound -​ Things move = ripples (waves) in the air -​ Rapid changes in air “pressure” Air waves and sounds -​ The human ear can detect pressure waves oscillating between 20-15,000 times per second (20-15,000 hertz) Hearing: Transduction -​ Multiple steps: the process by which some kind of energy is converted into signals in your nervous system (typically). Energy is snapping open molecules (opsin) causing downstream chemical reactions that open potassium channels. Matter pushing on other matter opens up ion channels in the somatosensory system 1.​ Outer ear: waves of air are filtered and funneled 2.​ Middle ear: Waves of air are converted into fluid waves 3.​ Inner ear: Fluid waves deflect a solid structure 4.​ The deflection is detected with mechanoreceptors Middle ear: Converts air waves into fluid waves -​ Eardrum - ossicles - cochlea -​ Ossicles: malleus, icus, stapes (the smallest bone in the body), pushes against another bone which eventually push on the cochlea resulting in oscillations The inner ear converts fluid waves into a mechanical signal -​ Fluid waves inside of the cochlea cause deflection of the basilar membrane -​ The basilar membrane moves relative to the tectorial membrane -​ The differential movement is detected by mechanoreceptors (hair cells) The mechanoreceptors are called hair cells, and make-up the “Organ of Corti” -​ Includes 3 rows of outer hair cells and 1 row of inner hair cells. Vibrations caused by sound waves bend the stereocilia on these hair cells via an electromechanical force Hair cells open up to let potassium and calcium channels which activate voltage gated calcium channels which cause the vesicles to fuse with the membrane and release neurotransmitters Movement differences between basilar and tectorial membrane cause the hair cells to bend Different parts of the basilar membrane are deleted by different wave frequencies Which of the following is an example of a mechanoreceptor? -​ Hair cells are mechanoreceptors as they detect mechanical change - open up ion channels or excite in some way Top-down - why might you want it at this level? Feedback connections? -​ Hear what sounds you want to focus on and what you want to ignore -​ Tune the volume (crowded spaces, you don't want to hear a big chirping, but if in a quiet place, you want to hear footsteps) -​ Control how well you want to hear things; ear itself can do this. There are multiple ways that auditory system modulates sound amplitude, ear can do this in three ways: 1.​ Neural signals to the ossicle muscles -​ Muscles can tighten or loosen depending on if you want to hear subtle changes (tight) - concert 2.​ Neural signals to the inner hair cells -​ 2 types (inner and outer hair cells) -​ The inner hair cells are different. They do less signals encoded but a lot of what they are doing is based on the volume, they push the tectorial membrane up or down, it can elongate to push the tectorial membrane  farther away or shorten to bring it closer in. That is how we regulate loud sounds vs soft sounds - the sensory receptors, make stuff go to the brain (volume) convert sound vibrations into electrical signals 3.​ Neural signals to the outer hair cells -​ Other neurons that come in and modulate how much depolarization comes in - neuromodulators, they inhibit the outer hair cells (or amplify them) which will change how much NT is released and how much signal you are getting -​ Other cells come in that are presynaptic that can inhibit and modulate an action potential -​ Amplify sound vibrations and enhance sensitivity Hearing: Anatomy -​ Ear -​ Brainstem (hindbrain) -​ Brainstem (midbrain) -​ Thalamus -​ Auditory cortex Auditory pathways in the cortex -​ Primary auditory cortex ​ Tonotopically organized - mapping ​ Highly plastic - can change easily -​ dorsal and ventral (“where” and “what”) pathways -​ Wernicke’s area (future lecture) ​ Links sound to word meanings. ​ Connected to area of frontal cortex for generating speech: (Broca’s area) Summary -​ Somatosensory ​ Mechanoreceptors (why so many types?) - receptive fields, adaptation ​ Open nerve endings (pain/temp) - hot vs. cold receptors - anterior cingulate cortex & pain inhibition ​ Somatosensory pathway: pain versus touch - thalamus - primary somatosensory cortex & somatotopic map (homunculus) - motor cortex -​ Auditory: ​ Air pressure waves  ​ Parts of the ear and their function - outer (filter & funnel air waves/vibrations) - middle (ear drum, ossicles, transmit air waves to create fluid waves) - inner (convert fluid waves to cell signaling) -​ Cochlea ​ tectorial & basilar membranes ​ mechanoreceptor “hair cells” ​ ear → brainstem → thalamus → cortex ​ primary auditory cortex & tonotopic map Lecture 10: Vestibular, Taste, and Smell The vestibular sense: sense of head movement and tilt (balance) - ear -​ Vestibular system: head moves one when you have a sense of gravity and know they everything is sitting the same way as before you just tilted your head -​ When in an Elevator, balance, vision and making sense of the visual world Transduction of Rotational Acceleration -​ Semicircular canals are tubes filled with endolymph fluid ​ When you have a tube with fluid and you rotate the tube, the water has inertia and the water will stay in place even though the tube is moving. If it rotates the endolymph fluid stays the same and doesn't move -​ Each canal contains a larger compartment: an ampulla ​ If tube and ampulla is moving and the water is staying put that means there is a solid pushing against it -​ The ampulla contains a gelatinous mass called a cupula -​ When the head turns, the cupula moves before the endolymph, the fluid pushes against the cupula causing it to deflect (bend). There are hair cells in the cupula and when it bends the hair cells will bend with them (same as the ear) -​ The cupula is inside the ampulla and the fluid inside, when you move the tube you move the cupula and ampulla and the fluid stays put, when the cupula moves the hair cells move and this causes releases of neurotransmitter on a postsynaptic cell. The cupula will move when you rotate your head, but the fluid inside will not move and pushes against the stuff that is moving Hair Cells in the cupula: mechanoreceptors -​ When the hair deflects you get an opening of ion channels that release neurotransmitters = action potential signals that go to brain stem Why 3 semicircular canals? -​ Linear acceleration: the utricle and saccule -​ 3 axes of movement, you want to be able to have access to movements, there are rotational movements that your head can make that have 3 different axes. Depending on direction different canales are responsible The Saccule and Utricle -​ Mechanoreceptors are in gelatin -​ Otoliths: in saccule and utricle -​ On top of the gelatin are crystals (otoliths) - sometimes called ear crystals (just heavy things, don't do anything) that sit on the gelatin mass and when you accelerate forward or backward or side to side, up and down, there is inertia because of this heavy stuff sitting on top of jelly, if you try and move it the crystals will not move. It will cause the hair cells to deflect by pulling the otolithic membrane back -​ Otoliths transduce linear acceleration and gravity -​ Saccual: gravity (up and down) -​ Utricle: linear acceleration (forward and backward) What is the Vestibular sense used for? - The chemical senses Taste (gustation) and smell (olfactory) allow direct detection of chemicals -​ Taste – chemicals in fluids/solids that provide information about edibility ​ They tell you about how edible that thing is, or you spit it out -​ Smell – chemicals in air that provide information about edibility/danger/social signals/etc - animals more often, humans use chemicals in the air if we wanna be there in that place Tastes are detected by the tongue -​ The tongue contains folds/bumps with distinct shapes called papillae -​ Papillae contain clusters of taste cells exposed by a pore, called taste buds. The papillae have folds and in the folds are pores that are taste buds made up of taste cells. Fluid gets in the pore and taste cells respond to different kinds of chemicals (tastes) in different ways  ​ Taste buds contain taste cells There are approximately 5 categories of taste (although “bitter” can be subdivided) -​ Sour: highly acidic substances - hydrogen ion channel (pH is low) ​ The hydrogens find their way through the pores and to change the relative ion concentrations because you have open hydrogen ion channels -​ Salty: substances with sodium - sodium ion channel ​ You mix the sodium with saliva and this i'll find its way to sodium channels through taste pores and will change the relative ion concentrations and depolarize the cell -​ Sweet: sugars and others - g protein receptor -​ Bitter: many different molecules - g protein receptor -​ Umami: glutamate - g protein receptors ​ Tomatoes, often meats, savory almost meaty flavor, if you eat glutamate it is not bad or good for you it's just a flavor -​ Some papillae have more of another taste, different proportions on the tongue for different tastes Where do taste signals go? - Gustatory Pathway 1.​ the solitary nucleus glands 2.​ Regions processing hunger, reward, aversion 3.​ The thalamus 4.​ Insular cortex -​ Taste regions of the brain are highly connected with reward/aversion regions Olfactory Transduction -​ Molecules in the air pass into the nose and land in the olfactory mucosa (slimy) this mucosa has nerve endings, the olfactory nerve is more of a number of axons that is just pushing themselves through the cribriform plate (separates olfactory bulb from the inner part of the nose) -​ Dendrites of olfactory cell neurons have metabotropic receptors -​ There are many different types of odor molecules, many different types of receptors Olfactory Pathways -​ Nose → olfactory bulb (where cell bodies are) -​ Olfactory bulb → primary olfactory cortex (reaches cortex BEFORE thalamus) -​ Insular cortex: combines olfactory and gustatory (flavors) - multimodal -​ Other:  ​ The Orbitofrontal Cortex (reward lecture) receives axons from multiple sensory areas to code reward values ​ Rhinal Cortices (memory lecture) receive convergent sensory information, important for forming abstract representations and forming memory Lecture 11: Movement Outline: Going backwards from the lecture... -​ Premotor cortex: Planning movements. Understanding Movements. Neurons fire before you start an action → Motor cortex. Coordinating movements → Brainstem and spinal cord. Coordinating movements. Like with circuits that create rhythms… → reflexes - Motor neurons “final common pathway” -​ Motor neurons → muscle cells (muscle fibers) How? (Remember -​ Acetylcholine and nicotinic receptors!) → depolarize muscle cells But wait, there’s more: -​ Proprioception: your sense of where your muscles are and what they’re doing - sensory system -​ The spinal cord is mostly sensory going posterior and more anterior is mostly motor - somatosensory travels up the spinal cord and makes its way into the brain. The central sulcus divides the front of the cortex from the posterior. The primary somatosensory system is just behind the sulcus -​ 2 pathways of signals - occipital parietal pathway: this is the “where” pathway (where info is dorsal). Then the temporal pathway “what” pathway. The Nervous System Controls Movement by Controlling Muscles -​ Our skeleton is covered in “skeletal muscles” - allow us to move around -​ Muscle fibers have myofibrils -​ Each myofibril can contract when depolarized - involves Ca+ The Neuromuscular Junction -​ Motor neuron axons synapse onto muscle fibers -​ The neuron releases acetylcholine, which binds to nicotinic receptors on the muscle - opens up sodium channels (ligand gated ion channels) and causes depolarization of muscles  -​ The axon is releasing (vesicular release) on a neurotransmitter which than acts on ligand gated sodium channels (nicotinic receptors is how we move) Motor Neuron -​ Motor neuron cell bodies are located in the ventral horn of the spinal cord - all the cell bodies are that have motor neurons -​ In the case of facial muscles, it is located in the brainstem nuclei How do we know what our muscles are doing? -​ Proprioceptive receptors: how we know where our body is and what our muscles are doing at a given time ​ Muscle spindles: sense muscle stretching ​ Golgi tendon organs: sense when motor neurons are depolarizing muscle cells - detecting when you're stimulating your muscles (when contracting them) Proprioception and Body Sense -​ Vibrator stimulates muscle spindles, giving the impression that the muscle is moving away from the face... and the nose is going with it! -​ Another exceptional Oliver Sacks case study: “The Disembodied Lady” - lost proprioception ​ Christina had “sensory neuritis,” lost her awareness of where her muscles were or how much they were contracting - jerking muscles ​ To others, she appeared insane ​ If you don't have the visual feedback, you think your nose is growing longer The Stretch Reflex -​ Green: if the stretch receptor gets info it will signal to the motor neurons in the ventral horn. Get more weight you get your sensory neuron sending signals to inhibit and excite -​ Geer dots: action potentials of the neurons Motor Control Loops -​ Reflexes: sensory signals → motor neurons -​ Spinal circuits: Sensory signals & top-down input are integrated → coordinate multiple muscles (motor neurons) (breathing and walking) -​ Brainstem nuclei: bottom-up and top-down signals are integrated to coordinate spinal circuits (plans made) -​ Cerebellum: motor coordination, sensorimotor learning, movement timing. If you had damage you would had damage tracking and moving stimulus -​ Motor cortex: coordinates movement through the brainstem and directly controls fine finger movements; main inputs from premotor and somatosensory cortices -​ Premotor cortex: coordinates movement through motor cortex, brainstem, spinal cord based on action plans -​ Prefrontal cortex: coordinates action plans based on context-dependent goals Example of Coordinated Movement: Locomotion -​ Locomotion is movements you don't really have to think about -​ When there is a repeated movement (one muscles contracts and other relaxes) and this is over and over again (walking, swimming) these are controlled by central pattern generators -​ Depends on multiple Central pattern generators neuron circuits that generate rhythmic activity -​ Spinal cord CPGs: cats can walk without a brain! - has enough sensory stimulation -​ Brainstem nuclei can initiate and halt locomotion -​ Brainstem nuclei are controlled by cortex & basal ganglia -​ Medial motor pathways - come from vestibular system, balance, posture -​ Superior colliculus - helping us orient to stimuli depending on what we want to orient to what is guiding our attention at a given time -​ Lateral - controls more of limb movements. Pathway is largely from cortex (red nucleus) Motor Cortex Controls Voluntary Movement -​ Neuronsin primary motor cortex, premotor, and even primary somatosensory cortex send axons to the spinal cord Primary Motor Cortex (M1) -​ A map of the body (“homunculus”), but not a clean one –lots of overlap between body parts very messy - somatotopically mapped -​ Stimulation of primary motor cortex can elicit specific postures, independent of the body starting position - doesn't matter where your arms started when you stimulated it would still end up in the same spot (what muscles should be contracted to elicit the movement) -​ If your somatosensory cortex is processing information about what is touching fingers, you want to have a fast ability to move fingers around for touch stimulus, so you have tiny axons that send signals to make fingers move Premotor Cortex -​ Ventral premotor cortex (in humans, includes Broca’s area) -​ Dorsal premotor cortex (supplementary motor area) -​ Supplementary motor area (SMA) - in medial wall - sequences ​ These regions signal information about actions based on “where” in space your body is moving (up, to the left, down) -​ Contains information about actions based on external space (e.g.: up, down, left) -​ “Mirror neuron” responses: neurons fire to action and to observation of action. - if you see someone perform action the neuron fires, or if you do the action the neuron will fire as well -​ SMA is important for movement sequences - (handshake, muscle memory) Rizzolatti, 1996: first discovery of mirror neurons -​ What information are mirror neurons signaling? (Hint, what are they NOT signaling?) -​ The black bars are how many times/trials -​ All the events are lined up in the middle across the trials -​ Raster Plot - way of seeing the correlation (temporal relationship) between when the neuron is firing action potentials and when the events of your experiment are happening -​ The neuron mirrors the experimenter putting it down, and then the monkey doing the same action. When the monkey makes a movement to pick it up the neurons fire a lot -​ Requires more than just visual input, the touch and proprioception (somatosensory system) - multimodal Organizing Principles of the Nervous System -​ The nervous system is organized in a hierarchy of loops: sensation → action (a.k.a. “reflex arcs”) -​ Sensory motor loops -​ You can integrate and combine information about the sensory world (detecting edges and lines) this can be put together to come up with actions (muscle contractions) A Voluntary Action -​ Neurons start firing in premotor cortex (planning and action), then in motor cortex (using the plans), then in parietal cortex, then primary sensory cortex - BEFORE the action?? ​ What would cause these parietal and sensory neurons to fire? - there are top down signals directly from the frontal cortex all the way back to the parietal cortex. The frontal regions (prefrontal, pre motor) don't just signal down to the spinal cord, they also signal back to the sensory system and set up an expectation. SOmetimes you set up the expectation and you move and your sensory system does something else (violate our expectations) ​ Ex: trying to tickle yourself - often doesn't work because you are already setting up the expectation (top down signals) from the motor system back to the sensory system. -​ Why would the sensory system be stimulated before the action starts? -​ Motor efference copy: ​ Motor cortex sends a copy of its output to sensory cortex ​ The frontal regions (prefrontal, pre motor) don't just signal down to the spinal cord, they also signal back to the sensory system and set up an expectation - anticipating Organizing Principles of the Nervous System -​ The nervous system is organized in a hierarchy of “reflex arcs” (sensory- motor/perception-action loops) The superior colliculus controls orientating, including eye movements - part of the medial (orienting) motor pathway in the body. Sends signals to eyes and core muscles. It is both bottom up input from the retina and top down signals -​ Saccades: jerky eye movements - sometimes they are microsaccades and sometimes we are trying to sample the visual world around us and they are bigger saccades -​ These saccades happen 150-250 ms apart - 6-12 saccades per second -​ Our eyes jerk from one place to another Saccade Movements -​ The superior colliculus controls eyes movements ​ suddenly (“jerk”) = saccade ​ gradual (smooth pursuit) ​ many neurons “vote” for where the eye should go (a “population code”) -​ Saccades automatically happen every ~1 s, but the frontal eye fields and supplementary eye fields also control them according to goals, & expectations -​ In your superior colliculus every neuron is participating in where your eyes are going to move next (kind of like a vote - move left, move right) and depending on where the input is coming from the right might have more activity and so that is voted stronger. A group of neurons all vote together “I wanna move there” Some Thought Questions 1.​ Can you walk without a brain? How? 2.​ Can you pick up an object without a brain? Why? 3.​ Why is the sensory system needed for movement? 4.​ Why are different spatial maps useful for computing movements? 5.​ In what way might eye movements be controlled in both a “bottom-up” and “top- down” way? Test 2 Review - Lecture 7-11 Lecture 7 - The Eye -​ Transduction - turning environmental energy into brain and body signals -​ Opsins -​ Mechanoreceptors - matter pushing against other matter -​ Retina - 3 layers: photoreceptors, bipolar cells, ganglion neurons, also horizontal neurons in between these areas and amicrean between bipolar and ganglion and horizontal between photoreceptors and bipolar -​ Information we see in the retina - cones are responsible for color (3 cones, trichromatic vision) -​ Horizontal neurons: think of lateral inhibition, center surround receptive fields, if you put the stimulus inside that center if will fire a lot but when you put it around the fired it wont fire as much -​ Amacrine Neurons: can be helpful for other kidneys of information that you can get from the retina. Color, speed and motion. Some retina ganglion cells will only fire in a certain direction. Some amacrine neurons are important for computing the proper response for which direction to go and speed. Lecture 8 - Vision  -​ The ganglion neurons send axons to the optic nerve and some of those axons cross to the other side of the brain, crossing through the optic chiasm. -​ Right information goes to the left side of the brain and vice versa. This crossing over happens at optic chiasm. -​ Thalamus - projects onto V1. multiple dimensions of organizations in V1, there are 6 layers of the cortex and different areas. You have some patches that signal color. The thymus tends to signal to layer 4. information and other blob areas that signal spatial information -​ Retinotopic map -​ Spatial signal: edges, organized in space they go from one part in space to another. Oriented line coding/responses -​ Orientational lines of spatial frequency - depends on pattern of activity -​ Blindspot -​ Dark current: you are photoreceptors (rods and cones) at rest they are spitting out neurotransmitters, but when you get light stimulating the opsins you get inhibition. So when you go into a dark room there is more current and more depolarization in the dark current of a dark place. Bipolar cells help translate this, when there is light there is hyperpolarization and you don't get as many neurotransmitter Lecture 9 - Somatosensory/Auditory System -​ These systems both use mechanoreceptors -​ Mechanoreceptors: transduction mechanism -​ Types of receptors -​ Different spatial and temporal scales -​ Adaptation -​ Proprioception (stretch receptors) uses mechanoreceptors -​ Signals ascend through spinalc rd then cross over to the other side of the brain, if theta retouch signs they cross over in brainstem -​ Touch to Brainstem to thalamus to S1 (primary somatosensory cortex) -​ Ventral horn: motor neurons -​ Dorsal horn: sensory - somatosensory goes to more dorsal parts of spinal cord -​ Hearing - the ear -​ outer ear the air waves get funneled and filtered until they hit the eardrum, which then is part of the middle ear which also has the ossicles (3 little bones) they are connect one after another and link the eardrum (air waves) to the cochlea (inner ear) in the cochlea there is fluid and hairs. The ossicles are bumping against and causing fluid waves, these waves of fluids push against the tectorial membrane and the basal membrane and when the fluid pushes against one relative to the other the hair cells in between them get bent (in the organ of corti) when the hairs get bent it opens up ion channels and causes a depolarization which causes neurotransmitter release which causes hearing  -​ The coclia is shaped as a spiral because it is tonotopically spiral -​ Tonotopic map - map of different tones (high frequency to low or vice versa) -​ Temp and pain - top down control of pain, frontal cortex has connection to brian stem then down to spinal cord that release opioids that inhibit the pain response -​ Different temp receptors and they bind to other receptors (heat sensor, cool sensor) Lecture 10 - Vestibular and Chemical Senses -​ Semicircular canals - in ear ​ Ampula - chamber that has the cupula which when you move it moves with you but the fluid of the circular canales pushes against it and moves the hair cells (fluid and hairs) -​ Utricle and saccule - in ear ​ They are detecting the linear movements either forward (utricle) or up and down movements, gravity (saccule) ​ The otoliths - ear crystals - this is the heavy thing on top that helps with inertia when moving forward ​ Endolymph - the fluid inside of something -​ Vitstubular detects changes in movement -​ Chemical senses - taste, olfaction ​ Taste: pupille have taste buds and taste buds have taste receptors/cells (pores) ​ Taste signals tend to go to primary taste cortex after going through brainstem and thalamus - insular cortex ​ Multimodal ​ Taste receptors ​ Salty - sodium ​ Hydrogen - sour ​ Sweet - g protein -​ Olfaction: metabotropic receptors, olfactory bulb, does not go through thalamus first goes through olfactory system first Lecture 11 - Movement -​ Proprioceptive Receptors - sensory organ - need to know where muscles are in order to move them -​ Muscle fibers how they contract when acetylcholine - neuromuscular junction uses acetylcholine on nicotinic receptors (metabotropic, logan gated ion channels) -​ Motor system sup to the brain -​ Reflexes -​ Hierarchy in motor system - sensory motor (reflexes and CPGs - central pattern generator in the CNS, it is generator rhythmic pattern - locomotion)  -​ Premotor cortex - motor cortex -​ Mirror neurons -​ Planning ction, and direction, sequences of action -​ Which region of pre motor cortex is important for planning the sequence of actions: supplementary motor SMAs Lecture 12: Reward Raster Plot -​ Window of time - make multiple rows, different rows of time -​ Records how the neuron is firing to something in the environment Reward - What is it? -​ Not a sensory stimulus (although stimuli can be rewarding) -​ Not a type of movement (although reward can initiate, suppress, and influence movements) - not something in the world -​ Not an emotion (although reward can initiate, suppress, and influence emotions) -​ “Reward” is a type of information, usually carried by sensory stimuli, that can cause approach and appetitive behaviours, can reinforce movements (cause them to be repeated), and can induce positive emotions Reward is Positive -​ A punisher (or negative reinforcer) is information, usually carried by sensory stimuli (painful, disgusting stimuli) that can cause and train avoidance behaviours and induce negative emotions Parsing Reward - How we Process Reward (3 main categories) -​ Liking (emotion) ​ Autonomic nervous system/visceral responses ​ Changes in facial expressions (smile when we like something) ​ Subjective reports of positive feelings - “I am happy about this” -​ Wanting (motivation) ​ “Stimulus-response” behaviors (approach behaviours - closer to a goal) ​ “Instrumental” behaviors to obtain reward - acting in certain weird ways in order to achieve a particular reward ​ Outcome-based plans - reflect on what might happen in the future and that can reflect you now -​ Reinforcement (learning)  ​ Learning to value stimuli/places/situations ​ Learning to perform certain movements ​ Learning outcomes -​ These functions are performed by different neural processes - sometimes in the same regions, sometimes different. Not always combined together, sometimes we want things that we don't really like -​ Sometimes overlapping sometimes not Reward Learning 1: Pavlovian (or classical) Conditioning (ivan Pavlov, late 1800s) -​ If you repeatedly present a valued stimulus after a neutral stimulus, an animal will show autonomic and motor responses to the neutral stimulus -​ Protocols where he could isolate specific stimuli (condition stimuli - light, sound) and an unconditioned stimulus (reinforcing- food, juice) autonomic responses. Then we learn to have these learned approached behaviours to the conditioned stimulus (dog salivating when he hears the sound) Reward Learning 2: Operant (or instrumental) Conditioning (B.F Skinner, early 1900s) -​ Animals will learn to repeat actions that lead to a valued stimulus. -​ At first these actions are specific to the valued stimulus (actions guided by expectations = action-outcome associations) -​ Gradually they become independent of the stimulus (habit: stimulus-response associations) -​ The operation responses start out as action outcomes (learning that if you do an action you get a certain outcome) After a while you stop thinking about it and it becomes a stimulus response (you just do it, habit) -​ Ex: Working in a factory that folds boxes, you know that if you fold more boxes in a specific way you get paid. The longer you do this it becomes a habit and you don't think about the reward for that anymore. (Olds and Milner): Electrical Stimulation to Some Brain Areas can be Used as the Reinforcement Signal -​ Most common region stimulated: The medial forebrain bundle or the lateral hypothalamus -​ Electrostimulation to some brain areas can be used for a reinforcement signal Wanting vs. Liking: Self Stimulation -​ ‘‘At its most frequent, the patient self-stimulated throughout the day, neglecting personal hygiene and family commitments... At times, she implored her family to limit her access to the stimulator, each time demanding its return after a short hiatus. During the past 2 years, compulsive use has become associated with frequent attacks of anxiety, depersonalization, periods of psychogenic polydipsia (excessive desire to drink without physical dehydration), and virtually complete inactivity.’’ (Portenoy et al., 1986; as quoted by Berridge, 2003) -​ Not something you want, is this like stimulation or does she want the stimulation? She wanted it but didn't like it. Which Regions of the Brain Process Reward Information? -​ Frontal cortex - medial