Brain and Behavior Review 1 PDF

Brain and Behavior Review 1 Instructor: Prof. Edward Korzus 1  Review focus: v 1. Nervous System Organization (Ch. 1) v 2. Computing with Neurons (Ch. 2.) v 3. Synaptic Plasticity (Ch. 3) Figure 1: Networks...

Brain and Behavior Review 1 Instructor: Prof. Edward Korzus 1  Review focus: v 1. Nervous System Organization (Ch. 1) v 2. Computing with Neurons (Ch. 2.) v 3. Synaptic Plasticity (Ch. 3) Figure 1: Networks on multiple spatial and temporal scales. Network neuroscience encompasses the study of very different networks encountered across many spatial and temporal scales. Starting from the smallest elements, network neuroscience seeks to bridge information encoded in the relationships between genes and biomolecules to the information shared between neurons. It seeks to build a mechanistic understanding of how neuron-level processes give rise to the structure and function of large-scale circuits, brain systems and whole-brain structure and function. However, network neuroscience does not stop at the brain, but instead asks how these patterns of interconnectivity in the CNS drive 2 and interact with patterns of behavior: how perception and action are mutually linked and how brain- environment interactions influence cognition. Finally, network neuroscience asks how all of these levels of inquiry help us to understand the interactions between social beings that give rise to ecologies, economies and cultures. Rather than reducing systems to a list of parts defined at a particular scale, network neuroscience embraces the complexity of the interactions between the parts and acknowledges the dependence of phenomena across scales. Box dimensions give outer bounds of the spatial and temporal scales at which relational data are measured and interactions unfold, and over which networks exhibit characteristic variations and dynamic changes. Inspired by an iconic image of neuroscience recording methods, last updated in ref. 1. ECOG, intracranial electrocorticography; EEG, electroencephalography; fMRI, functional magnetic resonance imaging; fNIRS, functional near-infrared spectroscopy; MEG, magnetoencephalography. 2  Brain and Behavior v Neuroscience is the scientific study of the brain. v Neuroscience is a multidisciplinary branch of biology that combines physiology, anatomy, molecular biology, developmental biology, cytology, mathematical modeling and psychology to understand the fundamental and emergent properties of neurons and neural circuits. v The Ultimate Challenge of Neuroscience: the understanding of the biological basis of learning, memory, behavior, perception, and consciousness Figure 1: Networks on multiple spatial and temporal scales. Network neuroscience encompasses the study of very different networks encountered across many spatial and temporal scales. Starting from the smallest elements, network neuroscience seeks to bridge information encoded in the relationships between genes and biomolecules to the information shared between neurons. It seeks to build a mechanistic understanding of how neuron-level processes give rise to the structure and function of large-scale circuits, brain systems and whole-brain structure and function. However, network neuroscience does not stop at the brain, but instead asks how these patterns of interconnectivity in the CNS drive 3 and interact with patterns of behavior: how perception and action are mutually linked and how brain- environment interactions influence cognition. Finally, network neuroscience asks how all of these levels of inquiry help us to understand the interactions between social beings that give rise to ecologies, economies and cultures. Rather than reducing systems to a list of parts defined at a particular scale, network neuroscience embraces the complexity of the interactions between the parts and acknowledges the dependence of phenomena across scales. Box dimensions give outer bounds of the spatial and temporal scales at which relational data are measured and interactions unfold, and over which networks exhibit characteristic variations and dynamic changes. Inspired by an iconic image of neuroscience recording methods, last updated in ref. 1. ECOG, intracranial electrocorticography; EEG, electroencephalography; fMRI, functional magnetic resonance imaging; fNIRS, functional near-infrared spectroscopy; MEG, magnetoencephalography. 3 Statistics: Human Brain v Weight - The weight of the human brain is about 3 lbs. v Neurons - Your brain consists of about 100 billion neurons. v Neuroglia – a glia:neuron ratio is less than 1:1 v Synapses - There are anywhere from 1,000 to 10,000 synapses for each neuron. 4  Brain Facts v Histology Brain cells can be broken into two groups: neurons and neuroglia. v Neurons, or nerve cells, are the cells that perform all of the communication and processing within the brain. Sensory neurons entering the brain from the peripheral nervous system deliver information about the condition of the body and its surroundings. Neuroglia, or glial cells, act as the helper cells of the brain; they support and protect the neurons. In the brain there are four types of glial cells: astrocytes, oligodendrocytes, microglia, and ependymal cells. v The tissue of the brain can be broken down into two major classes: gray matter and white matter. v Gray matter is made of mostly unmyelinated neurons, most of which are interneurons. The gray matter regions are the areas of nerve connections and processing. v White matter is made of mostly myelinated neurons that connect the regions of gray matter to each other and to the rest of the body. Myelinated neurons transmit nerve signals much faster than unmyelinated axons do. The white matter acts as the information highway of the brain to speed the connections between distant parts of the brain and body. 5  1.1 - How do neuroscientists study the brain? Gross anatomy of human brain: https://www.youtube.com/watch?v=OMqWRlxo1oQ&rco=1 More Detailed Analysis Neuroanatomical Techniques E.g., immunohistochemistry Fig. b1.1 Purple: antibody against arrestin, staining cones Orange/red: antibody against calbindin, staining amacrine, horizontal, and retinal ganglion cells Green: green fluorescent protein (GFP), expressed in bipolar cells of this transgenic mouse strain 6  Neurons – schematic (left) and real (right) Fig. 1.9 Major axon branches are called collateral Synapses are the places where one neuron contacts another neuron and communicates with it Myelin sheaths are produced by glial cells and “insulate” the axons by wrapping themselves around them More details in the next chapter 7  Axonal pathways are often “topographic,” and they often diverge and converge C. Negative feedback loops vs positive feedback loops Fig. 1.11 Topographic projection: adjacent neuron in one region project to adjacent neurons in another region Pathway divergence involves branching axons Pathway divergence often goes hand-in-hand with pathway convergence (when different axons project to a common target) 8  Neuronal circuits are rarely linear; they frequently diverge/converge and are often bidirectional Fig. 1.12 Illustrated here are some of the major visual pathways in mammals The red arrows indicate a simple linear pathway from the retina to the visual cortices, but the full circuit is more complex 9  Parallel sensory and motor hierarchies Association cortex sits at the highest level in both hierarchies Fig. 1.15 There are connections between the two hierarchies at multiple levels The motor system causes movements, which generally causes the input to the sensory system to change; in turn, sensations often lead to movement. 10  Do brains perform their core function “in series” or “in parallel” ? Fig. 1.17 In the vertical decomposition scheme, the brain performs multiple functions “in parallel” The more complex functions are layered on top of the simpler functions An actuator is a device that produces a motion by converting energy and signals going into the system. 11  The dual reflex arc model of Meynert & James (late 1800s) Fig. 1.13 A naïve infant learns to avoid touching the flame. Experience links two subcortical reflex arcs through transcortical connections: The experience of reaching for the flame and then withdrawing the hand in pain strengthens cortical “association fibers” (dashed arrows) that cause the perception of the flame to trigger withdrawal of the hand (before the hand can fully reach for the flame). 12  Summary: v The nervous system is hierarchically organized into molecules, cells, cell groups, major brain divisions, and central versus peripheral nervous systems. v Learning neuroanatomy requires learning many new terms. Among the most important are orientation terms such as dorsal, ventral, superior, inferior, ipsilateral, contralateral, sagittal, and coronal. v The central nervous system is divisible into brain and spinal cord. The brain comprises forebrain, midbrain, and hindbrain. These, in turn, consist of even smaller divisions. v The nervous system contains neurons and glial cells. The neurons have distinctive dendrites, axons, and synapses. Despite these specializations, only 1–2% of human genes are “brain-specific” 13  Ramon y Cajal’s use of the Golgi stain Cajal developed the “neuron doctrine” Fig. 2.1 The photograph in (A) shows Cajal sitting in his lab, surrounded by micro- scopes, chemicals, and specimens. The photomicrograph in (B) depicts a Golgi-stained neuron. Shown in (C) is one of Cajal’s detailed drawings of Golgi- stained neurons. The little arrows indicate the direction in which Cajal thought information flows; his inference turned out to be correct 14  Morphology of a Stereotypical Neuron Fig. 2.2 Panel (A) depicts an idealized neuron. The dendrites tend to become thinner with distance from the cell body. The axon gives off one major branch, called an axon collateral, and ends in a dense tangle of small branches. In contrast to dendrites, axons are uniformly thin and tend to branch at right angles. Panel (B) is a close-up of a typical neuronal cell body. Panel C shows several Nissl-stained neurons and glial cells 15  Ion concentrations inside and outside of a squid’s giant axon Table 2.1 Examples to remember as they may occur on the test Sodium and calcium ions are more concentrated outside of neurons than inside of them, whereas the reverse is true for potassium and most organic anions. Intracellular free calcium concentration is extremely low. 16  The Sodium-potassium Pump It moves 2 potassium ions into a neuron for every 3 sodium ions that it moves out, consuming 1 molecule of ATP Fig. 2.4 An Na/K-ATPase (red circle) pumps sodium ions out of the axons and potassium ions in. The process consumes metabolic energy provided by ATP. 17  Changes in Membrane Voltage and Ion Flow During each Action Potential Fig. 2.5 The neuronal membrane at rest is relatively impermeable to Na+, but some K+ flows out. During the rising phase of the action potential the membrane becomes highly permeable to Na+, which rushes down its concentration gradient into the axon and thus depolarizes it. Next comes the falling phase, during which the membrane becomes less permeable to Na+ and much more permeable to K+; this causes K1 to rush out of the cell, repolarizing it. Soon thereafter, K+ permeability returns to its resting level. When the membrane potential is more negative than its resting value, it is said to be hyperpolarized; this period 18 is called the action potential undershoot. 18  Action Potential Propagation Fig. 2.12 Action potentials travel along axons because the massive influx of Na+ ions at one location of the axonal membrane tends to trigger Na+ influx at adjacent locations, as long as those sites are not in the action potential’s wake (refractory). The top, middle, and bottom panels in this figure illustrate successive time points. The plus and minus signs represent ionic charges that have accumulated on either side of the axonal membrane (a plus on the inside indicates depolarization). The red arrows indicate ion flow. The graphs on the right show how membrane voltage varies along the length of the illustrated axons. 19  Myelin sheaths increase the speed of action potential propagation Fig. 2.14 (A) Saltatory conductions = saltatory means jumping (B) A myelin sheath wraps itself repeatedly around a myelinated axon. The axon remains unmyelinated at regularly spaced Nodes of Ranvier. (C) A myelinated axon at two points in time. Initially (top), Na+ rushes into the axon at a node of Ranvier, triggering a “pressure wave” of positive ions that travels down the axon. At the next node of Ranvier, the wave of current triggers another action potential (bottom). Na+ influx due to this second action potential triggers another wave of positive current, which flows both up and down the axon. However, current flow back up the axon does not trigger another action potential at the first node because 20 this node is now refractory. 20  Synapses release neurotransmitter molecules onto postsynaptic receptors Watch Video Clip: The Synapse Fig. 2.16 https://www.youtube.com/watch?v=L41TYxYUqqs When an action potential comes down an axon, Ca++ ions flow into the presynaptic terminal. This causes synaptic vesicles in the terminal to move toward the synaptic cleft and release glutamate. When glutamate binds to a postsynaptic glutamate receptor (of the AMPA type), the receptor allows Na+ ions to flow through its central pore into the postsynaptic cell. Shown on the right is an electron micrograph of a real synapse, showing presynaptic vesicles and the postsynaptic density, which is a dense meshwork of proteins that lines the postsynaptic side of the synapse. 21  Neurons integrate signals that they receive from presynaptic neurons over space and time EPSP = Excitatory Post-Synaptic Potential Spatial Summation Temporal Summation Fig. 2.17 Neurons integrate signals by receiving electrical impulses from multiple other neurons at their dendrites, summing up the combined electrical signals at the axon hillock, and then firing an action potential down the axon if the combined signal reaches a threshold, essentially "deciding" whether to send a signal further based on the total input received from other neurons; this process involves converting electrical signals into chemical signals at the synapse, where neurotransmitters are released to interact with receptors on the receiving neuron. When monitoring neuronal activity intracellularly at the cell body and activating synapses either close to the cell 22 body (proximally) or far out on the dendritic tree (distally), electric signals in the cell body resulting from proximal synapse activation are much larger than signals in the cell body due to distal input. Suppose two distal synaptic inputs are activated simultaneously. In that case, the two distal signals tend to sum when they reach the cell body, producing a single significant electric signal in the cell body that can trigger an action potential. This is known as spatial summation. The summation of small synaptic signals that occur in rapid succession is known as temporal summation. 22  Neurons can be modeled as “integrate-and-fire” devices Fig. 2.18 According to the integrate-and-fire model (A), neurons sum their inputs and then “fire” action potentials only if this sum exceeds a threshold, which is defined as a minimal level of activity that is required to trigger action potential (electrical impulse). Neurons function as precise coincidence detectors, i.e., if two or more presynaptic neurons fire action potential (electric impulse), then the neuron receiving these simultaneous signals (coincidence detection) will fire an action potential (electric impulse) itself. 23  Ionotropic vs. Metabotropic Receptors The receptor is an ion channel The receptor is coupled to an ion channel Fig. 2.22 Ionotropic receptors (top) let ions flow through their central pore when a transmitter is bound to them. In contrast, metabotropic receptors (bottom) do not contain an ion-passing pore. When metabotropic receptors are activated by a neurotransmitter, they activate enzymes that generate second messenger proteins, which in turn can open or close nearby ion channels. 24  The Prototypical Neuron ØThe Basic Structure of the Neuron Neuron A Neuron B 25 25  The Prototypical Neuron ØNeurons have 4 functional ZONES: (1) Input, (2) Integration, (3) Conduction, (4) Output Axon Hillock: Zone of Integration Axon: Zone of Conduction Terminal Bouton: Zone of Output Soma + Dendrites: Zone of Input 26 26  The Prototypical Neuron Three Different Types of Potentials: 1) Resting Potential (all ZONES) 2) Graded Potential (ZONES: Input) 3) Action Potential (ZONES: Integration, Conduction Watch Video Clip: https://www.youtube.com/watch?v=8- UBA_Ysgds 27 27 Brain and Behavior Neuronal Plasticity Instructor: Prof. Edward Korzus 28  Neuronal plasticity is frequently studied in “hippocampal slices” In such slices, several intra-hippocampal circuits remain intact Fig. 3.5 Shown at the top is a coronal section through a rat brain. The bottom diagram shows some major hippocampal divisions and connections. The yellow neuron projects from the dentate gyrus to one of the cornu ammonis (CA) fields. The red neuron projects to the dentate gyrus and the CA fields through the perforant path. 29  Long-term Potentiation (LTP) Discovered in 1973 by Bliss and Lømo Fig. 3.6 Bliss and Lømo (1973) recorded synaptic responses in the dentate gyrus of a rabbit’s hippocampus while applying four high-frequency (tetanic) trains of electrical stimuli to the perforant path (see Fig. 3.5). Already after the first tetanic stimulus, EPSP amplitude increased almost 100%. Importantly, some synaptic potentiation persisted for more than 10 hours after the stimulation. 30  Donald Hebb’s Famous “Rule” When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased. - Hebb, 1949. More simply: Neurons that fire together, wire together Bliss and Lømo (1973) recorded synaptic responses in the dentate gyrus of a rabbit’s hippocampus while applying four high-frequency (tetanic) trains of electrical stimuli to the perforant path (see Fig. 3.5). Already after the first tetanic stimulus, EPSP amplitude increased almost 100%. Importantly, some synaptic potentiation persisted for more than 10 hours after the stimulation. 31  The NMDA Receptor as a Molecular Trigger for LTP Because magnesium ions are dislodged from the NMDA receptor’s pore when the postsynaptic cell is strongly depolarized Fig. 3.8 If the post- synaptic membrane is near its resting potential (A), then NMDA receptors are blocked by magnesium (Mg++) ions; these ions are dislodged when the post- synaptic cell is strongly depolarized (B). Once the magnesium block is gone, Na+ and Ca++ ions can flow through the NMDA receptor when glutamate is bound. An increase in postsynaptic calcium then triggers an intracellular signaling cascade that ultimately leads to the insertion of additional AMPA receptors into the post- synaptic membrane, which strengthens the synapse. 32