Purve Neuroscience - Chapter Notes PDF

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Warning: TT: undefined function: 32 IntroductionNeuronsDendrites The number of inputs that a particular neuron receives depends on the complexity of its dendritic arbor o The number of inputs to a single neuron reflects the degree of convergence o The number of targets innervated to any one neuron r...

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Neuroscience Ch.1 Introduction Neurons Dendrites • The number of inputs that a particular neuron receives depends on the complexity of its dendritic arbor o The number of inputs to a single neuron reflects the degree of convergence o The number of targets innervated to any one neuron represents its divergence The presynaptic terminal is immediately adjacent to postsynaptic specialization of the target cell • Pre- and postsynaptic components communicate via secretion of molecules from presynaptic terminal that bind to receptors in the postsynaptic specialization through the synaptic cleft (site of extracellular proteins that influence the diffusion, binding, and degradation of molecules secreted by the presynaptic terminal) Axons • Specialized for relaying electrical signals; “reads” the information conveyed by synapses on the dendrites • Many types of axons o Relatively short axons = local circuit neurons (interneuron), found throughout the brain o Axons of projection neurons extend to distant targets (ex. axons from spinal cord to foot)  Uses action potentials that propagates from its point of initiation (axon hillock) to the terminus of the axon, at which point synaptic contacts are made Synaptic Transmission • Chemical and electrical process by which the information encoded by action potentials is passed on at synaptic contacts to the next cell in a pathway • Presynaptic terminals (axon terminals) and their postsynaptic specializations are typically chemical synapses – the most abundant type of synapse in the NS • Electrical synapses (facilitated by the gap junctions) are more rare Synaptic vesicles – spherical structures filled with NT molecules • The positioning of synaptic vesicles at the presynatpic membrane and their fusion to initiate NT release is regulated by a number of proteins w/in or associated with the vesicle • The NT released from synaptic vesicles modify the electrical properties of the target cell by binding to NT receptors localized primarily at the postsynaptic specialization • The intricate and concerted activity of NT, receptors, related cytoskeletal elements, and signal transduction molecules are the basis for nerve cells communicated with one another, and with effector cells in muscles and glands Neuroglial Cells Glial Cells • Neuroglial cells are more numerous than neurons in the brain (3:1), but don’t’ participate directly in synaptic interactions and electrical signaling • But, their supportive functions help define synaptic contacts and maintain the signaling abilities of neurons Roles • Maintaining the ionic milieu of nerve cells • Modulating the rate of nerve signal propagation • Modulating synaptic action by controlling the uptake of NT at or near the synaptic cleft • Providing a scaffold for some aspects of neural development • Aiding (or in some instances impeding) recovery from neural injury Types of Glial Cells • Astrocytes o Restricted to the CNS (ie brain and spinal cord) o Have elaborate local processes that give these cells a star like appearance

Neuroscience Ch.1 o Maintain an appropriate chemical environment for neuronal signaling o A subset of astrocytes in the adult brain may retain the characteristics of neural stem cells (capacity to enter mitosis and generate all of the cell classes found in the nervous tissue) • Oligodendrocytes o Also restricted to the CNS o Lay down a laminated, lipid-rich wrapping called myelin around some axons  Myelin has important effect on the speed of the transmission of electrical signals  In the PNS, the cells that elaborate myelin are Schwann cells • Microglial cells o Derived primarily from hematopoietic precursor cells o Share many properties with macrophages and are primarily scavenger cells that remove cellular debris from sites of injury or normal cell turnover o Also secrete signaling molecules (like their macrophage counterparts) – particularly a wide range of cytokines that are also produced by cells of the immune system – that can modulate local inflammation and influence cell survival or death Cellular Diversity in the Nervous System • The cellular diversity of any NS underlies the capacity of the system to form increasingly complicated networks and to mediate increasingly sophisticated behaviors • Can use fluorescent dyes and other soluble molecules injected into single neurons to visualize individual nerve cells and their processes • Other stains are used to demonstrate the distribution of all cell bodies – but not their processes or connections – in neural tissue o Demonstrate that the size, density, and distribution of the total population of nerve cells is not uniform form region to region within the brain o In some regions, such as the cerebral cortex, cells are arranged in layers and each layer has difference cell density Neural Circuits Neural circuits – process specific kinds of info and provide the foundation of sensation, perception, and behavior • The synaptic connections that define neural circuits are typically made in a dense tangle of dendrites, axon terminals, and glial cell processes that together constitute what is called neuropil • The neuropil = region b/w nerve cell bodies where most synaptic connectivity occurs Basic constituents of neural circuits • Afferent neurons – carry information from periphery toward the brain or spinal cord • Efferent neurons – carry information away from the brain or spinal cord (away from the circuit) • Interneuron – local circuit neurons, only participate in the local aspects of a circuit, based on the short distances over which their axons extend Myotatic Spinal Reflex • “Knee-jerk” reflex

Extracellular recordings – detect action poentials, usefully for detecing tempeoral patterns of action potential activity and relating those patterns to stimulation by othe inputs or to speciif behavioral events Intracellular recordings – detect the smaller, graded potential changes that trigger action potentials, and thus allow a more detailed analysis of communicaton between neurons within a cirut These graded triggering potentials can arise at either sensory receprs or synapses and are called receptor potentials or synaptic potentials, respectively

Neuroscience Ch.2 Electrical Signals of Nerve Cells Electrical Potentials across Nerve Cell Membranes • Resting membrane potential (-40 to -90 mV) • Receptor potentials – from the activation of sensory neurons by external stimuli such as light, sound, or heat o Ex. touching skin activates Pacinian corpuscles, receptor neurons that sense mechanical disturbances of the skin o Amplitudes are graded in proportion to the magnitude of the sensory stimulus • Synaptic Potentials – allows transmission of information from one neuron to another • Using electrical signals presents problems in electrical engineering o A fundamental problem for neurons is that their axons, which can be quite long are not good electrical conductors o To compensate for this deficiency, neurons have evolved a “booster system” that allows them to conduct electrical signals over great distances despite their intrinsically poor electrical character – action potentials • Action potentials – active response generated by neuron, when a brief change from negative to positive occurs in the transmembrane potential. o One way to elicit an action potential is to pass an electrical current across the neuron membrane  Current normally generated by receptor potentials or by synaptic potentials. In the lab, electrical current is produced by inserting a second microelectrode into the same neuron and then connecting the electrode to a battery o Amplitude of the action potential is independent of the magnitude of the current  All-or-none o Hyperpolarization – if current delivered makes membrane potential more negative  Nothing drastic happens; don’t require any unique property of neurons and are therefore called passive electrical responses o Depolarization – if current of the opposite polarity is delivered, so that the membrane potential of the nerve cell becomes more positive than the resting potential  In this case, at certain level of membrane potential, called threshold potential, and action potential occurs How Ionic Movements Produce Electrical Signals • Electrical potentials are generated across the membranes of neurons because… o There are differences in the concentrations of specific ions across nerve cell membranes o The membranes are selectively permeable to some of these ions • Active transporters – the ion concentration gradients are established by these proteins o Actively move ions into or out of cells against concentration gradients • Ion channels – only allows certain kinds of ions to cross the membrane in the direction of their gradient • Electrochemical equilibrium – there is an exact balance between two opposing forces: (1) the concentration gradient that causes ion (K+) to move from compartment 1 to compartment 2, taking along positive charge, and (2) an opposing electrical gradient that increasingly tends to stop K+ from moving across the membrane o The number of ions that needs to flow to generate this electrical potential is very small (~ 10-12 moles of K+ per cm2 of membrane)  Means that the concentrations of permeant ions on each side of the membrane remain essentially constant, even after the flow of ions has generated the potential  And the tiny fluxes of ions required to establish the membrane potential don’t disrupt chemical electro-neutrality because each ion has an oppositely charged counter-ion The Forces that Create Membrane Potentials • Equilibrium potential – electrical potential generated across the membrane at electrochemical equilibrium • Nernst equation = Equilibrium potential for any ion X

Neuroscience Ch.2

R=gas constant; T=absolute temperature (K); z=valence (electrical charge) of permeating ion; F=Faraaday constant (amount of electrical charge contained in one mole of a univalent ion) • When the concentration of K+ is higher inside than outside, an inside-negative potential is measured across the K+ permeable neuronal membrane • The balance of chemical and electrical forces at equilibrium means that the electrical potential can determine ion fluxes across the membrane, just as the ionic gradient can determine the membrane potential. Electrochemical Equilibrium in an Environment with More than One Permeating Ion o

Goldman’s Equation: o V = the voltage across the membrane; P = permeability of the membrane to each ion of interest o Extended version of the Nernst equation that takes into account the relative permeability of each of the ions involved The Ionic Basis of the Resting Membrane Potential • Action of ion transporters creates substantial transmembrane gradients for most ions o There’s much more K+ inside the neuron than outside, and much more Na+ outside than inside o These transporter-dependent concentration gradients are, indirectly, the source of the resting neuronal membrane potential and the action potential • Hodgkin and Katz Experiment: o Assuming that the internal K+ concentration is unchanged during the experiment, a plot of membrane potential vs. log(external K+ concentration) = straight line with slope of 58 mV per tenfold change in external K+ concentration at room temperature  Value not exactly 58 mV because other ions are also slightly permeable (Cl-, Na+) o Showed that the inside-negative resting potential arises because  The membrane of the resting neuron is more permeable to K+ than other ions  There is more K+ inside the neuron than outside • The selective permeability to K+ is caused by K+-permeable membrane channel that are open in resting neurons and the large K+ concentration gradients is produced by membrane transporters that selectively accumulate K+ within neurons The Ionic Basis of Action Potentials • If the membrane were to become highly permeable to Na+, the membrane potential would approach ENA • Hodgkin and Katz tested the role of Na+ in generating the action potential by asking what happens tot eh action potential when Na+ is removed from the external medium o Found that lowering Na+ concentration reduces both the rate of rise of the action potential and its peak amplitude • While the resting neuronal membrane is only slightly permeable to Na+, the membrane becomes extraordinarily permeable o Na+ during the rising phase and overshoot phase of the action potential o But very brief because increased membrane permeability to Na+ is very short-lived o Membrane potential rapidly repolarizes to resting levels and is followed by undershoot o During undershoot, the membrane potentials is transiently hyperpolarized because K+ permeability becomes even greater than at rest • The ion substitution experiments carried out by Hodgkin and Katz showed that the resting membrane potential results from a high resting membrane permeability to K+, and that depolarization during an action potential results from a transient rise in membrane Na+ permeability o But they did not establish how the neuronal membrane is able to change its ionic permeability to generate action potential, or what mechanisms trigger this critical change •

Neuroscience Ch.3 Voltage-Dependent Membrane Permeability Introduction • For most type of axons, the changes in membrane potential consist of a rapid and transient rise in sodium ion permeability, followed by a slower but more prolonged rise in permeability to potassium ions o Both permeabilities are voltage-dependent, increasing as the membrane potential depolarizes Ionic Currents Across Nerve Cell Membranes • Voltage clamp method = provides information needed to define the ionic permeability of the membrane at any level of membrane potential o Holds the membrane potential at a set point 1. Measures the membrane potential with a microelectrode placed inside the cell 2. Electronically compares this voltage to the voltage to be maintained (called the command voltage) 3. The clamp circuitry then passes a current back into the cell through another intracellular electrode 4. Permits the simultaneous measurement of the current needed to keep the cell at a given voltage a. This current = the amount of current flowing across the neuronal membrane, allowing direct measurement of these membrane currents • Voltage Clamp method can indicate how membrane potential influences ionic current flow across the membrane

Two Types of Voltage-Dependent Ionic Currents • No appreciable ionic currents flow at membrane potentials more negative than the resting potential. o At more positive potentials, however, the currents not only flow but also change in magnitude • The early current has a U-shaped dependence on membrane potential, increasing over a range of depolarization up to ~0mV but decreasing as the potential is depolarized further o At the Na+ equilibrium potential there is no net flux of Na+ across the membrane, even if the membrane is highly permeable to Na+ o No early current flows at the membrane potential where Na+ cannot flow is a strong indication that the current is carried by entry of Na+ into the axon o Removing external Na+  makes ENA negative; if the permeability to Na+ is increased under these conditions, current should flow outward as Na+ leaves the neuron, due to the reversed electrochemical gradient.  Found that removing external Na+ caused the early current to reverse its polarity and become an outward current at a membrane potential that gave rise to an inward current when external Na+ was present o Early inward current measured when Na+ is present in the external medium is due to Na+ entering • The late current increases monotonically with increasingly positive membrane potentials 1

Neuroscience Ch.3 Two Voltage-Dependent Membrane Conductances • Membrane conductance: the degree of permeability of a cellular membrane to certain ions; the reciprocal of the membrane resistance o Closely related, although not identical, to membrane permeability • Tetrodotoxin – neurotoxin found in puffer fish; blocks the Na+ current without affecting the K+ current o Tetraethylammonium ions block K+ currents without affecting Na+ currents • From the measurements, Hodgkin and Huxley found: o The Na+ and K+ conductances change over time  Ex. both Na+ and K+ conductances require some time to activate (turn on) • The K+ conductance has a pronounced delay, requiring several msec to reach max, whereas the Na+ conductance reaches max more rapidly  The more rapid activation of the Na+ conductance allows the resulting inward Na+ current to precede the delayed outward K+ current  Although the Na+ conductance rises rapidly, it quickly declines, even though the membrane potential is kept at a depolarized level • Shows that depolarization not only causes the Na+ conductance to activate, but also causes it to decrease over time (inactivate)  While the Na+ and K+ conductances are both time-dependent activated, only the Na+ conductance inactivates o Both the Na+ and K+ conductances are voltage-dependent  Both conductances increase progressively as the neuron is depolarized • The voltage clamp experiments carried out by Hodgkin and Huxley showed that the ionic currents that flow when the neuronal membrane is depolarized are due to three different voltage=sensitive processes: o Activation of Na+ conductance o Activation of K+ conductance o Inactivation of Na+ conductance Reconstruction of the Action Potential • To determine whether the Na+ and K+ conductances alone are sufficient to produce an action potential • Selective increase in Na+ conductance is responsible for action potential initiation • Rate of depolarization subsequently falls both because the electrochemical driving force on Na+ decreases and because the Na+ conductance inactivates o At the same time, depolarization slowly activates the voltage-dependent K+ conductance, causing K+ to leave the cell and repolarize the membrane potential toward E K . • Refractory period – caused by the relatively slow time to turn off the K+ conductance and the persistence of Na+ conductance inactivation • Positive feedback continues until Na+ conductance inactivation and K+ conductance activation restore the membrane potential to the resting level o This positive feedback loop is maintained by the voltage-dependence of the ionic conductances • The properties of the voltage-sensitive Na+ and K+ conductances, together with the electrochemical driving forces created by ion transporters, are sufficient to explain action potentials Threshold • Initiation of the action potential  positive feedback loop • The depolarizing “trigger” can be one of several events: a synaptic input, a receptor potential generated by specialized receptor organs, the endogenous pacemaker activity of cells that generate action potentials spontaneously, or the local current that mediates the spread of the action potential down the axon • Subthreshold depolarization – within which the rate of increased sodium entry is less than the rate of potassium exit o Where Na+ inflow = K+ outflow = unstable equilibrium like the ignition point of an explosion • There is no specific value of membrane potential that defines the threshold for a given nerve cell in all circumstances Long-Distance Signaling by Means of Action Potentials 2

Neuroscience Ch.3 • A depolarizing stimulus – a synaptic potential or a receptor potential in an intact neuron, or an injected current pulse – locally depolarizes the axon, thus opening the voltage-sensitive Na+ channels in the region • Opening of Na+ channels causes inward movement of Na+  depolarization of the membrane potential  action potential o Some of the local current generated by the action potential will then flow passively down the axon o This passive current flow depolarizes the membrane potential in the adjacent region of the axon, thus opening the Na+ channels in the neighboring membrane • Action potential propagation requires the coordinated action of two forms of current flow: the passive flow of current as well as active currents flowing through voltage-dependent ion channels • Refractoriness limits the number of action potentials that a neuron can produce per unit time, with different types of neurons having different maximum rates of action potential firing due to different types and densities of ion channels o Ref...