Brain and Behavior Notes PDF

1/13/25 Monday Brain’s Primary Function: ​ Produce behavior ​ To do this, it must receive info about the world, integrate that info to create perception and produce commands to control movement (muscles) CNS: ​ Brain and spinal cord PNS:...

1/13/25 Monday Brain’s Primary Function: ​ Produce behavior ​ To do this, it must receive info about the world, integrate that info to create perception and produce commands to control movement (muscles) CNS: ​ Brain and spinal cord PNS: ​ Sensory neurons get info from the outside world and send it to the spinal cord and brain ​ Motor neurons sense stuff out ​ All of the processes radiating out beyond the brain and spinal cord Neurons: ​ The nervous system is composed of neurons (discrete cells) ​ Neurons in the brain communicate with one another, sensory receptors in the skin, muscles, and internal body organs Cortex: ​ Heavily folded outer layer of brain tissue composed of neurons ​ Complex thinking (humans are larger than other animals) ​ Also called the cerebrum, forebrain, and cerebral cortex ​ Prominent in mammals and birds ​ Responsible for most conscious behaviors Brainstem: ​ The source of behavior in simpler animals ​ Responsible for most of our unconscious behaviors Behavior: ​ Animals produce behaviors that are either inherited ways of responding or learned ​ Most human behavior consists of a mix of inherited and learned actions ​ The complexity of behavior varies considerably from species to species ​ The more complex the nervous system = the wider the range of behavior ​ The more simple the nervous system is = the narrower the range of behavior Anatomical Divisions of the Nervous System: Somatic Nervous System: ​ Soma = Body ​ Aware of the things happening to your body (conscious) Autonomic Nervous System: ​ Automatic  ​ Not aware of things (subconscious) Enteric Nervous System: ​ Gut system Afferent Information: ​ Sensory information coming into/towards the CNS (incoming information) Efferent Information: ​ Information leaving the CNS (outgoing info) ​ A comes before E (sensory info has to come in before you can move) ​ SAME (Sensory Afferent, Motor Efferent) Brain-Body Orientation (in relation to the midline): ​ Dorsal: structures atop the brain or a structure within the brain (dorsal fin) ​ Ventral: structures towards the bottom of the brain or one of its parts (a vent is in the floor) ​ Lateral: structures located towards the sides (my ear is lateral to my nose) ​ Medial: structures towards the brain’s midline (my nose is more medial than my eye) (medial/middlel) ​ Anterior/rostral: front (towards the nose) (rostral/nostril) ​ Posterior/caudal: back (behind you, back of your head) ​ Proximal: towards the center core (close to you) (proximal/proximity) ​ Distal: away from the center core (far away from you) (distal/distance) 1/15/25 Wednesday Cuts: Coronal ​ Cutting the face from the head ​ Cut in a vertical plane ​ From the crown of the head down ​ Yielding a frontal view of the brain's internal structures ​ Cannot see posterior ​ Most dorsal and ventral Horizontal ​ Cutting off the top of the head ​ The view of the cut falls along the horizon ​ It is usually viewed looking down on the brain from above (dorsal view) ​ Can see the most lateral or medial (at least the midline) ​ Most rostral(anterior) and caudal(posterior) Sagittal ​ A cut between the two ears ​ Cut lengthways from front to back and viewed from the side ​ Imagine the brain split by an arrow  ​ A cut in the midsaggital plane divides the brain into symmetrical halves (a medial view) ​ Most dorsal and ventral Cerebral Cortex: ​ The brain is split into 2 hemispheres ​ Every area of the brain has a mirror of itself in each hemisphere ​ The cerebral cortex is made up of two sets of four lobes ​ Temporal = smell ​ Occipital = vision ​ Frontal = decision making, personality, motor cortex (in front of the dividing line between frontal and parietal) ​ Parietal = sensory cortex Sulcus (sulci): ​ A groove (a wrinkle in) in brain matter ​ Central sulcus = from the most dorsal down to ventral on the lateral side (boundary from frontal to parietal lobe), RED LINE ​ Parieto-Occipital sulcus = in between the boundary between the parietal and occipital lobe Gyrus (gyri): ​ A protrusion or bump (outwards) formed by folding of the cerebral cortex ​ Precentral gyrus = motor cortex, where voluntary motor movements are created ​ Post central gyrus = somatosensory cortex, touch and pain Fissure: ​ A very deep sulcus ​ Lateral fissure = (Sylvian) on the lateral side by the boundary between the frontal lobe and temporal lobe and the temporal lobe from parietal, RED LINE ​ Longitudinal Fissure = splits the two cortical hemispheres Dorsal View → ` Terms Regarding Neuron Pathways: Ipsilateral: ​ Same side ​ EX: My left eye is ipsilateral to my left ear Contralateral: ​ Opposite side ​ EX: If you have a lesion in the left occipital lobe, you will experience symptoms in the contralateral visual field/right side of vision) Bilateral: ​ Both sides ​ EX: When the spinal cord is severed completely, the patient’s body will be affected bilaterally, both sides paralyzed Decussate: ​ (If a neuron or pathway) crosses the midline Olfactory Bulbs - Smell Optic Chiasm - Where visual info decussates Pons - Sleep, regulatory processing Brainstem - (medulla) breathing, heart rate Cerebellum - Ballance Made from a midsaggital cut (to get a medial view) Neuron Internal Features in the Brain Gray Matter: ​ Areas of the nervous system that are mostly composed of cell bodies and blood vessels ​ Gray because of all the organelles in the cell body as well as the blood vessels (keeping it alive) ​ If in the CNS - Nuclei ​ If in the PNS - Ganglion White Matter: ​ Areas of the nervous system rich in neural axons (tracts) ​ Fatty substance = white ​ Bundles of axons going somewhere else ​ If in the CNS - Tract ​ If in the PNS - Nerve Corpus Callosum ​ Made up of white matter (going from one hemisphere to the next) ​ White matter tracts that connect the two cortical hemispheres (how they communicate) ​ Only for the cortex (4 lobes), not brain stem and other structures ​ It contains about 200 million axons (so the body can coordinate with itself) ​ Without it, each hemisphere acts like its own brain ​ The biggest tract in the brain Four Ventricles/Cavities: ​ Cavities in the brain that contain cerebrospinal fluid (CSF) ​ CSF = Sodium chloride and other salts ​ CSF is made by choroid plexus ​ Two lateral ventricles (left & right) ​ Third ventricles ​ Fourth ventricles ​ They flow into each other Ventricular System: ​ How the brain gets rid of the ‘trash’ it accumulates during the day (byproducts from work) ​ It is a system to keep the brain nourished ​ The ventricular system is filled with CSF and is lined with the choroid plexus that produces it, fills subarachnoid space (fluid) to surround/cushion the brain Flow: lateral ventricles (make csf) → flow into third ventricle at the midline → flow into cerebral aquaduct → flow into 4th ventricles → down spinal cord 1/17/25 Friday Brain Protection - The Meninges Layers of the Brain (in order) 1) Dura Mater: ​ “Hard mother” ​ Outermost layer ​ Tough outer layer of fibrous tissue ​ The thickest layer of the meninges 2) Arachnoid Layer: ​ Like a spider web ​ A thin sheet of delicate connective tissue ​ Filled up with CSF (protect the brain from hitting the sides of the skull) 3) Pia Mater: ​ “Soft mother” ​ Moderately tough inner layer that clings to the brain’s surface ​ 1-cell thick, cannot see with eyeball Top-down = dorsal view Meningitis ​ An infection of the meninges that can lead to pressure on the brain and spinal cord ​ Causes meninges to deteriorate Subarachnoid Lymphatic-like Membrane (SLYM): → ​ A newly discovered layer of the meninges​ ​ It seems to aid the cerebral spinal fluid in removing waste from the brain ​ Within the subarachnoid space Meninges In The Spinal Cord: The Circle of Willis: ​ The brain needs oxygen and gets it from the blood, it is made up of communicating arteries ​ (on the left) It's a ventral view. Two vertebral arteries (bottom by the brain stem) eventually merge into one called the basilar artery (as seen in the middle one), The Circle of Willis is the circle in the middle that provides the blood to the cerebral arteries  ​ (in the middle) four pairs of cerebral arteries (called anterior cerebral artery, middle cerebral artery, posterior communicating artery, and posterior cerebral artery) ​ (on the right) Input of blood into the Circle of Willis/vascular system ← if there is a blood clot within this area = stroke ← if there is a blood clot in the circle of Willis (in the posterior communicating arteries) = no stroke symptoms (still have blood flow) Brain ProtectionBlood-Brain Barrier: ​ A network of blood vessels and cells that protect the brain from toxins (drugs and toxins cannot cross this barrier unless it is small enough to fit through a transporter or otherwise pass through the cells that are creating tight junctions) ​ Not all brain regions are protected by the BBB! (regions under the ventricles do not have BBB protection) ​ No pores (right junctions), do not allow things to come in or out easily ​ Blood vessels have transport systems that allow certain things to come in and out (ex: glutamate) (a drug can sneak along with glutamate or if it is fat soluble) ​ Area Postrema - The part of your brain that detects toxins and causes you to vomit The Central and Peripheral Nervous Systems: ​ Spinal vs Cranial Orientations: Cross-section of Spinal Cord: ​ White and gray matter ​ Gray matter = nuclei ​ Axons = tracts The Spinal Cord: ​ The different sections of the spinal cord connect with the limbs and organs at their corresponding level ​ EX: Upper thoracic parts of the spinal cord control movement and receive sensory info from the arms ​ Between the vertebrae, there are afferent nerves coming out (because going towards the CNS) but if they went away from the CNS they would be called efferent Dermatomes and Myotomes ​ Each spinal nerve is responsible for detecting sensations in the area of the body they are coming out from ​ Motor spinal nerves control the muscles in that area of the body Dermatomes ​ The areas of skin that send signals through a specific spinal nerve root Myotomes ​ Muscle groups that receive signals through a specific spinal nerve root ​ Efferent ​ EX: C1/C2 – neck extension/flexion, C6/C7 – elbow extension/flexion, L3 – knee extension The Spinal Nerves: ​ Originates in the spinal cord – control functions of the rest of the body Afferent nerves: relay sensation from the body to the CNS Efferent nerves: send out motor commands from the CNS to the body ​ Dorsol most half of the spinal cord = sensory info (getting things in) ​ Ventral most half of the spinal cord = motor info (sending things out) There is a Dorsal Root Ganglion - (cell bodies of sensory neurons/cells) transmits sensory information from the body to the central nervous system (CNS) - (it is the bulge above the arrow that points to the Ventral root)​ 1/22/25 Wednesday The Cranial Nerves ​ 12 nerves ​ Enter and leave on ventral surface of the brain (most in brainstem) ​ Carry sensory & motor info ​ Eye, tongue and facial movements ​ Vision, Hearing, Taste ​ Swallowing ​ Vagus Nerve = control of organs – longest nerve of the autonomic nervous system, to relax you ​ *mixed somatic and autonomic* (mostly somatic) Recap: Tracts: Bundles of axons in the CNS Nuclei: groups of cell bodies of neurons in the CNS Nerves: Bundles of axons in the PNS (outside the CNS) Ganglia: Groups of cell bodies of neurons in the PNS The Autonomic Nervous System Sympathetic Nervous System ​ Cell bodies located in the middle areas of the spinal cord ​ Send information to sympathetic ganglia (groups of cell bodies), which then act as a unit ​ “Fight or Flight” Parasympathetic Nervous System ​ Cell bodies located at the top and very bottom of the spinal cord ​ “Rest and Digest” ​ Relax Act as a unit (ganglion chain) → Development of The Human Brain ​ The brain is split up into subdivisions called encephalon ​ The neural tube will eventually become the ventricle system 3 Major Divisions of The Brain  1)​ Forebrain: Telencephalon, Diencephalon 2)​ Midbrain: Mesencephalon 3)​ Hindbrain: Metencephalon, Mylencephalon The Forebrain: Consists of the telencephalon and the diencephalon Telencephalon: ​ Lateral ventricle ​ Cerebral cortex (named after the bark on a tree) ​ Corpus Callosum ​ The outer layer of neural tissue ​ Basal ganglia ​ Limbic system Diencephalon (“interbrain”): ​ Third ventricle ​ Thalamus – relay station, sleep/wakefulness ​ Hypothalamus - regulation of visceral activities, metabolic processes, vital functions (hunger, thirst...) Limbic system - emotions, memory Basal Ganglia - movement The Midbrain (mesencephalon): It consists of the tectum and tegmentum Important for initiation and control of movement and for goal-related behaviors Tectum (roof over the brain stem/cerebral aqueduct) ​ Contains parts of the brain that help guide orientation to sights and sounds (made up of the superior and inferior colliculi) Tegmentum (floor of the cerebral aqueduct) ​ Contains the midbrain inputs to the basal ganglia and limbic system The Hindbrain: The oldest part of the brain It consists of the medulla oblongata (myelencephalon) and the pons and cerebellum (metencephalon) Metencephalon: ​ Cerebellum: sensorimotor and balance ​ Pons: sleep and arousal Myelencephalon: ​ The medulla is involved in the control of essential life processes (heart and respiratory function) → damage to the medulla = death  1/24/25 Friday Cells of the Nervous System Glial Cells (or Glia): ​ Provide support, structure, and nourishment for neurons ​ ~ 75% of the total number of cells that make up our brain are glial cells Neurons: ​ Specialized cells that are capable of sending and receiving chemical signals ​ Main communicators of the nervous system (both in PNS & CNS) ​ ~86 billion neurons in the human brain ​ There are 3 structural classes of neurons (polarity/how many “things” come out of its cell body) – Multipolar, Bipolar, Monopolar ← Polarity: ​ Refers to the number of processes (out-growths) coming from the cell body (including all axons and dendrites) ​ Multipolar = greater polarity (more things coming out of the cell body) ​ Monopolar = less polarity (one thing coming out of the cell body) ​ Bipolar = medium polarity (two things coming out of the cell body) Four Types of Glia Astrocytes: ​ In the CNS ​ The biggest glial cell ​ Very numerous ​ Star-shaped, symmetrical ​ Structural support for neurons ​ Scar tissue formation ​ Synapse isolation ​ Transports substances between neurons and capillaries (blood-brain barrier) ​ Makes sure that the message sent between neurons ONLY gets to the right neuron (synaptic isolation/isolates synapses) Microglia: ​ In the CNS ​ The CNS’s immune cells ​ Similar to peripheral macrophage ​ Mostly found in gray matter (where the cell bodies are, need to be protected bc very important) ​ Drives and reduces inflammation, attacks infections, activates T-cells ​ Swells up and attacks bacteria (engulfs it) ​ Green (in the pic) Oligodendrocytes: ​ In the CNS ​ One can provide myelin for multiple axons ​ The myelin/white matter around axons (fatty substance) ​ Nodes of Ranvier (gaps in between myelin sheaths/exposed axons) ​ Short stretches of many axons ​ Multiple sclerosis Schwann Cells: ​ In the PNS ​ Same function as the Oligodendroctyes ​ Provides myelin for one axon ​ Nodes of Ranvier ​ Multiple sclerosis Neuronal Anatomy: ​ Neurons are information processors – they collect information, process/integrate information, and transmit information to other neurons ​ Dendrites - Collect information ​ Cell body (soma) - Integrates information ​ Axon - Integrates and transmits ​ Axon Terminals - Transmit information ←Diversity of Shapes and Sizes:  Three Functions of Neurons Sensory Neurons: ​ Collect inf ormation from a bodily source Interneurons (association neurons): ​ Many branches collect info from many sources Motor Neurons: ​ Pass information on to command muscles to move The Neuron Doctrine: ​ Santiago Ramόn y Cajal (1859-1934) ​ The nervous system is made up of discrete individual cells ​ Used a Golgi stain to look at neurons ​ “Contiguous, not continuous” Parts of a Neuron (yellow highlight means add in notes) The Soma/Cell Body: ​ Nucleus - contains DNA (genetic code) ​ Many things for the neurons are made in the Soma ​ Enzymes to synthesize proteins, receptors, and neurotransmitters ​ Enzymes to provide energy and nutrients to the cell ​ Waste disposal ​ Without a cell body, the neuron would die - can’t grow back a cell body Dendrites: Input Zone ​ Receive information/input from other neurons/sensory systems ​ Extend from the cell body ​ Contain receptors for/detects neurotransmitters ​ Branched to receive input from different neurons ​ Where chemical information from the environment is detected and converted to electrical information ​ Sends information to the cell body where it is integrated ​ Dendritic Spines: Protrusions from dendrites where incoming neurons make contact/send a chemical signal →  1/27/25 Monday More Parts of a Neuron Axon: Conduction Zone ​ Conduct electrical information from the cell body to the end of the neuron ​ Extend from the cell body ​ Information is electrical (involving the movement of charged ions) ​ It can be short (in the brain) or very long (from the brain down the spinal cord) ​ It can be wrapped in myelin (fatty tissue) which speeds up signal conductance minimizes signal decay & myelin provides insulation Axon Terminal (buttons or boutons or end-feet): Output Zone ​ Transmit information to other neurons ​ Contain packages of neurotransmitters (vesicles) ​ Release neurotransmitters, when signal from axon, arrives ​ Neurons can have multiple axon terminals→ Send signals to multiple places ​ Terminals can make contact with dendrites, axons, and other terminals ​ Multiple axon terminals coming from one axon ​ Direct control - many axon terminals going to one place Cell Membrane - Lipid Bilayer: ​ 2 layers of fat molecules ​ Separates intracellular (inside cell) and extracellular fluid (outside cell) ​ Proteins (receptors, channels, transporters) span the membrane, communicating from the outside of the cell to the inside ​ (Ion channels: Pores that enable ions to pass across the membrane) The Synapse: ​ Communication between two neurons ​ The synapse is the connection between an axon terminal (presynaptic cell) and the dendrite or soma of another cell (post-synaptic cell) ​ The two neurons are not physically in contact with one another ​ There is a small space between them (the synaptic cleft) ​ The cell that sending the signal through the axon terminal = presynaptic cell ​ Synaptic Cleft (gap between the axon of one neuron and the dendrites of another neuron) ​ EX: The yellow one in the top left (presynaptic cell) sending the signal to the blue one (postsynaptic cell)  ​ Receiving cell = postsynaptic cell Parts of a Neuron and Their Roles in Neuronal Communication Chemistry Review Not Going to be on a Test, But Should Know Ion: ​ Elements ​ Naturally occurring substances ​ Three main ones: Oxygen, Carbon, and Hydrogen (these make up more than 90 percent of a cell’s composition) ​ Atom - smallest quantity of an element that retains the properties of that element ​ Ion - electrically charged atom (some positively, some negatively) Resting Membrane Potential: ​ A neuron at rest is a balance of electrochemical forces ​ An electrical-potential difference across the cell membrane ​ At rest, there is an uneven distribution of + and – ions across the cell membrane ​ Thus, there is a difference in electrical charge between the inside and outside of the neuron (membrane potential) (KNOW) ​ At rest, the difference in electrical charge is -70 mV (can range between -50 to -80mV) inside versus the outside→ resting membrane potential ​ The inside of the neuron is more negative relative to the outside (by 70 mV) Ions: ​ Electrically charged molecules ​ They can be positively charged (e.g., Na+, K+, Ca++) ​ They can be negatively charged (e.g., Cl-) ​ Ions are dissolved in intracellular fluid, separated from the extracellular fluid (CSF) by the cell membrane (Lipid bilayer) Resting Ion Gradients: When a neuron is not firing action potentials or being stimulated by other neurons, we say that the neuron is at rest At Rest - inside of the cell is -70 The resting potential of most neurons is about -55 to -80 mV, meaning that the inside of the cell is more negatively charged than the outside. At Rest ​ More sodium (Na+) is found outside the cell (in CSF) than inside the cell ​ More potassium (K+) is found inside the cell than outside the cell ​ More chloride (CI-) is found outside the cell than inside the cell ​ More calcium (Ca2+) is found outside the cell than outside the cell At Rest (-70) ​ Sodium Channels (Na+) are closed (open up at -50) ​ Electrostatic pressure wants to push chloride (Cl-) outside of the cell ​ The concentration gradient wants to push potassium (K-) outside of the cell ​ Chloride Channels (Cl-) are open Measuring the Resting Membrane Potential: Establishes the Resting Membrane Potential: 1) Concentration Gradients 2) Electrostatic Pressure 3) Membrane Permeability 4) Active Ion Transport 1)​ Concentration Gradients: ​ Chemical driving force ​ “Diffusion” ​ Particles in random motion tend to move from areas of high concentration to areas of low concentration 2) Electrostatic Pressure: ​ Electrical driving force ​ ”Opposites attract” ​ Like charges repel each other (+ repels +; - repels -) ​ Opposite charges attract each other (+ attracts -) ​ Inside is negative, sodium is a charged ion - attracted ​ Chloride is the only negative one, so it is attracted to the outside of the cell/CSF CSF of the cell 3) Membrane Permeability: Ion channels ​ the ion channels contributing to the membrane potential are “voltage-gated” (open and close when the membrane potential reaches a particular voltage) At rest ​ Voltage-gated Na+ channels are mostly closed (require membrane potential to be about -50 mV to open) ​ Some K+ channels (leaky) are open (will be opened at - 90 mV or higher) ​ Cl- channels are open (opened by -70 mV or higher) 4) Active Ion Transport: Na+/K+ (sodium-potassium) Pump ​ Not Ion channels (those are passive) ​ The transport system works against sodium and potassium (chucks it out of it detects and binds) ​ A transporter that uses energy to pump 3 Na+ ions out for every 2 K+ ions in ​ -Na+/K+ pump counteracts the forces driving Na+ in by pumping it back out  ​ - Na+/K+ pumps counteract the forces driving K+ out by pumping it back into ATP ​ Energy (ATP) for the Na+/K+ pump is provided by mitochondria (one of the organelles in the cell body ← Selectively Permeable Ion Channels: What is Really Happening at Rest - K+: ​ K+ (potassium) wants to leave ​ Highly concentrated inside wants to go to an area of lower concentration ​ K+ (is a positive ion) so it is attracted to the inside of the cell (-70) ​ Passive concentration gradient (more K+ inside) ​ Electrostatic pressure to keep K+ ions in (more – on the inside); but slightly less than the concentration gradient ​ Some K+ channels are open /“leaky” so there is less resistance to K+ ions leaving ​ The cell is constantly leaking out K+ ​ BUT Na+/K+ pump keeps pumping them back inside 1/29/25 Wednesday What is really happening at rest - Cl-: ​ Find it outside, through concentration gradient, pushed inside ​ CI- is repelled by the inside of the cell (-70) ​ Cl-: in equilibrium Electrostatic pressure forces Cl- out (more – on the inside) ​ As Cl- accumulates outside, a passive concentration gradient moves it back inside ​ Cl- channels are open at rest so no resistance to them crossing the membrane ​ Only ion at equilibrium when the cell is at rest (concentration gradient is still outside trying to push it in while electrostatic pressure is pushing it out) ​ Cl- entry/exit is held in equilibrium when the neuron is at rest What is really happening at rest - Na+: ​ Na+: wants to enter the cell (-70) ​ Passive concentration gradient (more Na+ outside) ​ Electrostatic pressure (because Na+ is + and attracted to the – inside of the neuron) ​ Most stay out because Na+ channels are closed ​ What gets in is pumped out by the Na+/K+ pump ​ Kicking out 2 sodium for every 3 potassium it brings in, going against passive concentration, kicking it out At Rest: ​ Na+ channels are mostly closed (require membrane potential to be about -50 mV to open) ​ Leaky K+ channels are open (will be opened at -90 mV or higher) ​ Cl- channels are open (opened by -70 mV or higher) Neuron-Neuron Communication: ​ The Synapse: The point where one neuron comes into contact with another neuron ​ There is a little space separating the neurons: Synaptic Cleft ​ Neurotransmitters (chemicals synthesized in and released from neurons) are released from the axon terminals of the presynaptic neuron (before the synapse; the “sending” neuron) ​ Receptors for neurotransmitters are located usually on the dendrites of the postsynaptic neuron (after the synapse; the “receiving” neuron)  Electrical Effects of Receptor Activation Hyperpolarization: ​ An increase in membrane potential—the interior of the cell becomes even more negative, relative to the outside. Depolarization: ​ A decrease in membrane potential—the interior of the cell becomes less negative. Postsynaptic potentials (PSPs): ​ Brief changes in the resting potential resulting from synaptic input. Inhibitory postsynaptic potential (IPSPs): ​ Produces a small local hyperpolarization Excitatory postsynaptic potential (EPSPs): ​ Produces a small local depolarization Electrical effects of receptor activation - IPSPs and EPSPs Local Potentials: ​ As the potential spreads across the membrane, it diminishes as it moves away from the point of stimulation Graded Responses: ​ The greater the stimulus the greater the response ​ Amount of neurotransmitter released Number of receptors activated 1/31/25 Friday Inhibiting Electrical Effects of Receptor Activation - HYPERPOLARIZATION: ​ IPSPs can make the inside of the cell more negative relative to the outside ​ → hyperpolarization (movement of positive charge/ions out or negative charge/ions in) (more negative) Exciting Electrical Effects of Receptor Activation - DEPOLARIZATION:  ​ EPSPs make the inside of the cell more positive relative to the outside ​ → depolarization (movement of positive charge/ions in or negative charge/ions out) (more positive) Really Exciting Electrical Effects of Receptor Activation – Action Potential: ​ The signal that the postsynaptic cell sends ​ Cell fluctuates away from resting potential (-70mV) ​ If more positive than negative = reach a threshold ​ Sodium Ion Channels = closed when the cell is at rest, opened when the cell is -50mV ​ EPSPs (positive ions) make the cell move from a -70 to -50 (activation threshold) ​ Depolarization to get from -70 to -50 ​ As pos and neg ions disperse through the neurons, they reach the voltage-gated sodium channels, if -50, they open and sodium goes inside ​ Sodium has a concentration gradient (attracted to inside of the cell/negative environment), which is why it rushes inside the cell when the channels open ​ Axon Hillcock = first place with voltage-gated Sodium channels ​ Dendrites and cell bodies are constantly integrating EPSPs and IPSPs ​ If the sum of the EPSPs and IPSPs reaches the “threshold of activation” in the junction between the cell body and the axon→ the neuron will “fire” an action potential ​ Threshold of activation= depolarization of about 10- 20 mV (so the neuron goes from -70 mV to -60 mV or -50 mV) Action Potential Properties: ​ Massive momentary (~1 msec) reversal of the membrane potential (from -70 mV to +50 mV) ​ A rapid change in electrical potential going from neg→pos→neg ​ (-70→+50) ​ All-or-none property of action potentials: the neuron fires at full amplitude or not at all. This does not reflect increased stimulus strength (a neuron will either fire or a signal or it will not) ​ Action potentials increase in frequency with increased stimulus strength. Integrate synaptic inputs: ​ Neurons perform information processing to integrate synaptic inputs ​ A postsynaptic neuron will fire an action potential if a depolarization that exceeds the threshold reaches its axon hillock. ​ Could need a combination of A and B, then have enough of the charge moving down to reach the hillock Spatial Summation: ​ Spatial summation is the summing of potentials that come from different parts of the cell ​ If the overall sum—of EPSPs and IPSPs—can depolarize the cell at the axon hillock, an action potential will occur ​ Remember that EPSPs and IPSPs are local Scenario: ​ The integration of PSPs arriving at different parts of the neuron ​ You have 4 presynaptic neurons synapsing on a postsynaptic neuron ​ Neurons A and B activate excitatory receptors→EPSP ​ Neurons C and D activate inhibitory receptors→IPSP ​ When Neurons A and C fire simultaneously, (EPSP and IPSP) they would cancel each other out and they would be equal Temporal Summation: ​ Temporal summation is the summing of potentials that arrive at the axon hillock at different times ​ The closer together in time that they arrive, the greater the summation Scenario: ​ The integration of PSPs arriving at different times ​ You have 2 presynaptic neurons synapsing on a postsynaptic neuron ​ Neuron A activates excitatory receptors→EPSP ​ What happens when neuron A fires rapidly? Accumulation of positive ions ​ Neuron B activates inhibitory receptors→IPSP ​ What happens when Neuron B fires rapidly? Accumulation of negative ions Neurotransmission Gated Ion Channels (what opens ion gates): ​ Leaky channels are ungated (always open) ​ Voltage-gated channels are opened (or closed) when Vm falls into some target range ​ Ligand-gated channels are opened (or closed) when a chemical molecule binds to them (such as a neurotransmitter, hormone, drug, second messenger molecule, etc.)  ​ Mechanically gated channels are opened (or closed) by a mechanical force such as physical touch, vibration, etc ​ Optically gated channels are opened (or closed) by light The Ionic Basis of the Action Potential: ​ Action potential - massive momentary (~1 msec) reversal of the membrane potential (from -70 mV to +50 mV) – an electrical signal generated at the axon hillock that moves down the axon towards the axon terminal ​ Action potentials are generated when the threshold of activation (a depolarization of about 5-20 mV) occurs around the axon hillock (from -70 mV to -50 mV) ​ The threshold of activation – – Voltage that opens voltage-gated Na+ channels (-50mV) in the area of the axon hillock→ Na+ comes rushing in making the membrane potential depolarize all the way up to +50 mV ​ Activated ligand-gate Na+ channels allow Na+ to rush in and depolarize the membrane causing an EPSP ​ If the sum of all the EPSPs and IPSPs are large enough to reach threshold, the voltage-gated Na+ channel open near axon hillock ​ The influx of Na+ is so large that the efflux (moving out) of K+ (through leaky channels) during the depolarization phase does not alter the effect of Na+ on the membrane potential ​ The influx of Na+ (Na+ moving into the neuron) activates voltage-gated K+ channels that allow K+ to flow out – the repolarization phase ​ When the neuronal membrane becomes very depolarized (about +50 mV), the Na+ channels close – Voltage-gated channels have thresholds for opening as well as closing ​ Voltage-gated K+ channels are slow to close→ keep spitting out K+, (potassium keeps leaving) dropping the membrane potential BELOW the resting membrane potential (hyperpolarization (undershoot phase) ​ Sodium pouring in the cell → peak (+50), then voltage-gated sodium channels close and the potassium channels open up, potassium leaves the cell (bc positive inside and potassium is positive & very concentrated) → potassium channels slow to close, which leads to hyperpolarization (undershoot phase) ​ When the neuronal membrane is hyperpolarized (i.e., below resting membrane potential), the neuron is now that much further away from the threshold of action ​ Relative refractory period: time when it is possible to fire another action potential but only if you apply greater than normal stimulation (at the undershoot)  ​ To trigger an axion potential during the undershoot, you need more EPSPs (to make up the difference) ​ Absolute refractory period: time when it is impossible to fire another action potential (after threshold all the way to the peak) 2/3/25 Monday Propagation of the Action Potential: ​ Once generated at the axon hillock, the action potential travels WITHOUT DEGRADING down the length of the axon – All or none! ​ The action potential does not degrade because there are so many sodium channels covering the axon right up to the terminal buttons ​ Chain reaction ​ How a neuron can keep the same signal down the axon without degrading, triggering down the axon Glia – Schwann cells and Oligodendrocytes: ​ Myelination: speeds up electrical signal ​ Saltatory Conduction: “jumping” of electrical signal from node to node ​ Production of myelin sheaths around axons ​ Myelin: fatty insulation around axons Velocity of the Action Potential: The speed of the action potential down an axon depends upon 2 main factors: 1)​ Thickness of the axon: thicker = faster - decreased internal resistance to passive current flow 2)​ Myelination: saltatory conduction, concentrated Na+ channels in the nodes of Ranvier, involves passive, instant signaling Long axons typically are large & Myelinated (e.g., motor neurons=200 mph) Propagation of the Action Potential: ​ Na+ entry locally depolarizes the axon ​ Alters the membrane potential in the adjacent area→triggering the threshold for activation of Na+ channels and the massive depolarization happens again in the adjacent area of the axon  ​ Refractory periods keep the action potential going in one direction ​ Have to open up channels at every point along the axon to keep the signal going (regenerates signal as it goes), but it slows along the signal (at each Node of Ranvier - see this happen) ​ Start at the axon hillock, voltage-gated sodium channels up, sodium comes in and disperses within areas of lower concentration, the ones that go down the axon encounter more voltage-gated sodium channels (more sodium comes in), more sodium encounters more channels, only opens up the channels that are going to the axon terminal (only can trigger the ones that haven't been activated yet/ refractory period) ​ Na+ entry locally depolarizes the axon ​ Myelin prevents K+ leakage out ​ Depolarization at the next node opens Na+ channels to regenerate the action potential ​ Nodes of Ranvier: small gaps in myelin occurring approximately every millimeter along an axon Disorder Affecting Myelination - Multiple Sclerosis: ​ An auto-immune disease where your body attacks its own myelin MS Disorder affects myelination ​ Characterized by the degeneration of myelin, resulting in neuronal death and the formation of plaques (hardenings) in the brain and spinal cord ​ Disruption in fast, saltatory conductance; sometimes loss of conductance altogether ​ Results in weakness, paralysis or spasms, impaired coordination, visual problems, etc. Synapse Configurations: ​ The majority of synapses in the brain are axo-dendritic (axon terminals synapse with dendrites or on dendritic spines) ​ Axo-axonic synapses can allow for the regulation of neurotransmitter release from the targeted axon terminal Input Location and Strength: ​ The distance between the synapse and axon hillock is inversely proportional to the “strength” of the synapse – the ability of a given input to elicit action potential  ​ EPSPs and IPSPs degrade as they move within the neuron ​ What kind of synaptic configuration would influence the postsynaptic neuron more? ​ Axosomatic synapses tend to influence the postsynaptic neuron more than axodendritic synapses 2/5/25 Wednesday Neurotransmitter release – transmission at chemical synapses: ​ The axon terminal – the electrical signal of the action potential is converted into a chemical signal Neurotransmitters: ​ Must be made and released from a Neuron/cell ​ A chemical, gas, or hormone that is synthesized in and released from a NEURON ​ Large neurotransmitters (e.g., peptides and hormones) = synthesized in the soma and then transported down the axon to the terminal (microtubules-railway system) ​ Small neurotransmitters (e.g., amino acids, monoamines, acetylcholine and gasess - synthesized in the terminals ​ In the terminal, most neurotransmitters are stored in membranes called VESICLES ​ RELEASE of a neurotransmitter occurs when vesicles “dump” neurotransmitters into the synaptic cleft Neurotransmission - Exocytosis: → Neurotransmitter release – action potential frequency: ​ Action potentials increase in frequency with increased stimulus strength ​ The higher the frequency of action potentials arriving at the terminal, the greater the influx of Ca2+ and the more vesicles releasing neurotransmitters into the synaptic cleft Ending Neurotransmission: ​ Neurotransmission requires precise timing Timing is controlled by 4 mechanisms: 1) Transmitter degradation (enzymes) 2) Transmitter removal through reuptake transporters 3) Autoreceptor activation - regulates calcium channels and the machinery involved in exocytosis (regulates how many neurotransmitters get released) 4) Diffusion - neurotransmitters simply move out of the synaptic cleft; a minor mechanism in CNS Autoreceptors: ​ Receptors that are located on the edges of the active zone on the presynaptic terminal; regulate calcium channels and the machinery involved in exocytosis ​ Activated = less exocytosis/neurotransmitter release Neurotransmitter action on the post-synaptic neuron: Transmitter Receptors: Ionotropic Receptors ​ Ligand-gated ion channel ​ Fast transmission ​ Neurotransmitter binds directly to the receptor ​ Channel opens immediately Ions flow across the membrane for a brief time Metabotropic Receptors ​ Indirectly linked with ion channels through signal transduction mechanisms ​ G protein-coupled receptors (GPCRs) ​ Slower transmission ​ Neurotransmitter binds a G protein-coupled receptor ​ G protein becomes activated ​ G protein binds to an adjacent ion channel Metabotropic receptors II ​ G protein-coupled receptor ​ Slowest transmission ​ Neurotransmitter binds a G protein-coupled receptor G protein becomes activated ​ G protein activates a second messenger ​ Second messengers act on ion channels and other cellular targets ​ 3 steps to get there ​ Travels down to the soma ​ It can open up ion channels and make cellular changes to the cell ​ * Second messenger: Slow-acting signaling molecule that amplifies and ​ The neurotransmitter binds to metabotropic receptor → activates G protein in the cell → G protein splits into subunits – one subunit goes to enzyme → enzyme triggers second messenger → second messenger can open up an ion channel OR go to the cell body and affect it cellularly ←Transmitter receptors - summary: Neurotransmission – Gap Junctions (Electrical synapses): ​ A specialized type of synapse between two excitable cells, e.g., cardiac muscle cells, some smooth muscle cells, and some neurons ​ Ions flow from one neuron directly into the other ​ 0 time delay ​ No neurotransmitter required ​ Good for synchronous activation of muscle fibers 2/7/25 Friday Signal Versatility ​ Any given neuron can release only a few types of neurotransmitters but can receive and respond to many more kinds of neurotransmitters. ​ Receptor subtypes—the same neurotransmitter may bind to a variety of subtypes, which trigger different responses. If you take any given neuron, that neuron only produces one neurotransmitter (most specialized for making and releasing one neurotransmitter) BUT it can receive signals from many different neurotransmitters (dendrites receive many different signals) For any given neurotransmitter a master key opens up a ton of different receptors that are all for that particular neurotransmitter (ex: the master key is dopamine to open a dopamine receptor NOT serotonin) (receptor subtypes) Molecule (serotonin) could be causing immediate EPSP if ionotropic receptors BUT if only metabotropic serotonin would have a different effect–IPSP A lot of IPSPs slow down the action potential (decrease the number) A lot of EPSPs speed up the action potentials (increase the number) Receptor Subtypes: A given neurotransmitter can have effects on a variety of receptor subtypes ​ Some inhibitory, some excitatory ​ Some ionotropic, some metabotropic Inhibitory effects ​ Reduce the number of action potentials in the postsynaptic cell (usually through ligand-gated Cl- channels) Excitatory effects ​ Increase the number of action potentials in the postsynaptic cell (usually through ligand-gated Na+ channels) Cellular changes can occur with repeated or absence of receptor activation ​ Ex: many nonstop EPSPs = overstimulated → take away some receptors ​ Same for IPSPs ​ Basis of tolerance and drug use