Purve Neuroscience - Chapter Notes

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 Refractory behavior ensures polarized propagation of action potentials from their usual point of initiation near the neuronal cell body, toward the synaptic terminals at the distal end of the axon • As the action potential sweeps along the length of an axon, in its wake the action potential leaves the Na+ channels inactivated and K+ channels activated for a brief time Increased Conduction Velocity as a Result of Myelination • Conduction velocity – a measurable rate of transmission that the action potential has o Defines the time required for electrical information to travel from one end of a neuron to another and, thus, limits the flow of information within the nervous system • One way to improve passive current flow is to increase the diameter of an axon, which increases the internal resistance to passive current flow • Another way to improve passive flow of electrical current is to insulate the axonal membrane reducing the ability of current to leak out of the axon and thus increase the distance along the axon that a given local current can flow passively  myelination of axons o Oligodendrocytes in the CNS (and Schwann cells in PNS) wrap the axon in myelin  Myelin – consists of multiple layers of closely opposed glial membranes o Speeds up because action potential generation occurs only at specific points along the axon, called nodes of Ranvier  Voltage-gated Na+ channels required for action potentials are found at these nodes  Saltatory – meaning the action potential jumps from node to node 3 Neuroscience Ch.4 Ion Channels and Transporters Ion Channels Underlying Action Potentials • Based on ionic conductances and currents measured in voltage clamp experiments, the postulated channels had to have several properties o Because the ionic currents are quite large, the channels had to be capable of allowing ions to move across the membrane at high rates o Because the currents depend on the electrochemical gradient across the membrane, the channels had to make use of these gradients o Because Na+ and K+ flow across the membrane independently of each other, different channel types had to be capable of discriminating between Na+ and K+ o Given that the ionic conductances are voltage-dependent, the channels had to be able to sense the voltage drop across the membrane, opening only when the voltage reached appropriate levels • Experimental work established that transmembrane proteins called voltage-sensitive ion channels exist and are responsible for action potentials and all of the other electrical signals previously described • Evidence for the presence of voltage-sensitive, ion-selective channels in nerve cell membranes o From the measurements of the ionic currents flowing through individual ion channels  The voltage-clamp apparatus used by Hodgkin and Huxley could only resolve the aggregate current resulting from the flow of ions through many thousands of channels o Used Patch Clamping – way to test individual ion channels The Patch Clamp Method • Cell-attached patch clamp recording method o The seal between the pipette and membrane becomes so tight that no ions can flow between the pipette and the membrane o So, all the current that flows when a single ion channel opens must flow into the pipette • Whole-cell recording o If the membrane patch within the pipette is disrupted by briefly applying strong suction, the interior of the pipette becomes continuous with the cell cytoplasm o Allows measurements of electrical potentials and currents from the entire cell o Also allows diffusional exchange between the solution in the pipette and the cytoplasm, producing a convenient way to inject substances into the interior of a “patched” cell • Inside-out patch recording configuration o A small vesicle of membrane to remain attached to the pipette o By exposing the tip of the pipette to air, the vesicle opens to yield a small patch of membrane with its (former) intracellular surface exposed o Makes it possible to change the medium where the intracellular surface of membrane is exposed o Valuable when studying the influence of intracellular molecules on ion channel function • Outside-out patch recording configuration o If the pipette is retracted while it is in the whole-cell configuration, the membrane patch produced has its extracellular surface exposed o Optimal for studying how channel activity is influenced by extracellular chemical signals such as neurotransmitters • Microscopic currents are due to the opening of single, voltage-activated Na+ channels o First, the currents are carried by Na+ and directed inward when the membrane potential is more negative than E NA; outward at more positive potentials, and reduced in size when the Na+ concentration of the external medium is decreased o Second, the channels have a time course of opening, closing, and inactivating that matches the kinetics of macroscopic Na+ currents Neuroscience Ch.4 • The channels open mostly at the beginning of a prolonged depolarization, showing they inactivate • Both the opening and closing of the channels are voltage-dependent; so the channels are closed at -80mV but open when the membrane potential is depolarized • Tetrodotoxin, which blocks the macroscopic Na+ current also blocks microscopic Na+ currents • Some properties of the channels: o Ion selectivity – Na+ and K+ channels are able to discriminate between Na+ and K+ o Because their opening is influenced by membrane potential, both channels are voltage-gated o Depolarization increases the probability of channel opening; hyperpolarization closes them o Also have voltage sensors that detect the potential across the membrane Toxins That Poison Ion Channels A) Effects of toxin treatment on frog axons. (1) α-Toxin from the scorpion prolongs Na+ currents recorded with the voltage clamp method. (2) As a result of the increased Na+ current, α-Toxin greatly prolongs the duration of the axonal action potential. Note the change in timescale after treating with toxin. (B) Treatment of a frog axon with β0toxin from another scorpion shifts the activation of Na+ channels, so that Na+ conductance begins to increase at potentials much more negative than usual. The Diversity of Ion Channels • Studies have found many voltage-gated channels that respond to membrane potential in much the same way as do the Na+ and K+ channels that underlie the action potential • Other channels, however, are gated by chemical signals that bind to extracellular or intracellular domains on these proteins and are insensitive to membrane voltage Voltage-Gated Ion Channels • In mammalian neurons, a voltage-sensitive Na+ channel that does not inactivate has been identified o This channel gives rise to a “persistent” Na+ current that helps regulate action potential threshold and repetitive firing o This channel serves as a target of local anesthetics such as lidocaine • Ligand-Gated Ion Channels • Activated by binding neurotransmitters • These channels are essential for synaptic transmission and other forms of cell-cell signaling • Whereas the VG ion channels underlying the action potential typically allow only one type of ion to permeate, channels activated by extracellular ligands are usually less selective, allowing more ions through • Other ligand-gated channels are sensitive to chemical signals arising within the cytoplasm of neurons and can be selective for specific ions such as K+ or Cl-, or permeable to all physiological cations o Distinguished by ligand-binding domains on their intracellular surfaces that interact with second messengers such as Ca2+, cAMP, or protons Neuroscience Ch.4 o Main function of these channels is to convert intracellular chemical signals into electrical info  Important in sensory transduction, where intracellular second messenger signals associated with sensory stimuli – such as odors and light – are transduced into electrical signals by cyclic nucleotide-gated channels • Although many ligand-gated ion channels are located in the cell surface membrane, other are found in the membranes of intracellular organelles such as mitochondria or ER The Molecular Structure of Ion Channels • They are all integral membrane proteins that span the plasma membrane repeatedly • Na+ and Ca2+ channel proteins consist of repeating motifs of six membrane-spanning regions that are repeated four times (total of 24 transmembrane regions) o Na+ or Ca2+ channels can be produced by just one of these proteins, although accessory proteins, beta subunits, can regulate the function of these channels • K+ channel proteins typically span the membrane six times, though there are some that span the membrane only twice, 4X, 7X • Most VG ion channels also contain a distinct type of transmembrane helix that possesses a number of positively charged amino acids and serves as the voltage sensor that detects changes in the electrical potential across the membrane • The structure of the pore is well suited for conducting K+; the narrowest part is near the outside mouth of the channel and is so constricted that only a non-hydrated K+ ion can fit through the bottleneck o Larger cations cannto traverse this region o And smaller cations like Na+ cannot enter the pore because the pore “walls” are too far apart to stabilize a dehydrated Na+ ion o This part of the channel complex is responsible for the selective permeability to K+  selectivity filter • Water-filled cavity that connects to the interior of the cell o Collects K+ from the cytoplasm and, utilizing negative charges from the protein, allows K+ ions to become dehydrated so they can enter the selectivity filter o These “naked” ions are then able to move through four K+ binding sites within the selectivity filter to eventually reach the extracellular space • Ion channels are integral membrane proteins with characteristic structures that allow them to conduct ions, to sense the transmembrane potential, to inactivate, and to bind to various neurotoxins Active Transporters Create and Maintain Ion Gradients • Nerve cells restore ions displaced during the current flow that occurs as a result of both neural signaling and the continual ionic leakage that occurs at rest o Done by active transporters • Active transporters form complexes with the ions they’re translocating. o Ion translocation by active transporters is much slower than ion movement through channels • ATPase pumps – acquire energy direction from the hydrolysis of ATP o Most prominent example of an ATPase pump is the Na+ pump o Responsible for maintaining transmembrane concentration gradients for both Na+ and K+ • A second class of active transporter does not use ATP directly but instead uses the electrochemical gradients of other ions as an energy source o Carry one or more ions up its electrochemical gradient while simultaneously taking another ion down its gradient o 1. Ion Exchangers – exchange intracellular and extracellular ions  Ex. Na+/Ca2+, Na+/H+ o 2. CoTransporters – carry multiple ions in the same direction  Na+/K+/Cl- co-transporter and K+/Cl- co-transporter • Although the electrochemical gradient of Na+ is the proximate source of energy for both ion exchangers and co-transporters, these gradients ultimately depend on the hydrolysis of ATP by ATPase pumps such as the Na+/K+ ATPase pump Functional Properties of the Na+/K+ Pump • Pump transports 2K+ into the cell for every 3 Na+ that are removed Neuroscience Ch.4 • But b/c pumps act much more slowly than ion channels, the current produced by the Na/K pump is small Neuroscience Ch.7 Molecular Signaling Within Neurons Strategies of Molecular Signaling • Paracrine signaling – acts over a longer range than synaptic transmission and involves the secretion of chemical signals onto a group of nearby target cells • Endocrine signaling – secretion of hormones into the bloodstream, where they can affect targets throughout the body • Chemical signaling requires three components: o A molecular signal that transmits info from one cell to another o A receptor molecule that transduces the information provided by the signal o A target molecule that mediates the cellular response • Intracellular signal transduction – the part of this process that takes place within the confines of the target cell o Ex. binding of the NT norepinephrine to its receptor activates GTP-binding proteins, which produces second messengers w/in the postsynaptic target, activates enzyme cascades, and eventually changes the chemical properties of numerous target molecules w/in the affected cell • Example of transduction in the context of Intercellular Communication o The sequence of events triggered by chemical synaptic transmission: NT serve as signal, NT receptors serve as transducing receptor, and the target molecule is an ion channel that is altered to cause the electrical response of the postsynaptic cell • Signal amplification – second messenger molecules (cyclic AMP) • These complex signal transduction schemes permit precise control of cell behavior over a wide range of times o Some molecular interactions allow info to be transferred rapidly, others are slower and last longer • Ch.9: Touch and Proprioception Afferent Fibers Convey Somatic Sensory Information to the CNS • Sensory transduction – the process of converting the energy of a stimulus into an electrical signal o Stimulus alters the permeability of cation channels in the afferent nerve endings, generating a depolarizing current (receptor potential) o If enough magnitude, the receptor potential reaches threshold for the generation of action potentials in the afferent fiber  The resulting rate of action potential firing is roughly proportional to the magnitude of the depolarization • Afferent fibers are often encapsulated by specialized receptor cells called mechanoreceptors that help tune the afferent fiber to particular features of somatic stimulation o Encapsulated endings have lower thresholds for action potential generation. Therefore, they are more sensitive to sensory stimulation than are free nerve endings • Afferent fibers that lack specialized receptor cells = free nerve endings o Important in the sensation of pain • Axon  spinal cord • Neurite  towards the fingertip o So when you pinch your finger, you’re activating neurite endings to initiate action potentials that goes to the ganglion cell body and then to the spinal cord/axon then to the brain to be interpreted  Sodium channels sitting at end of neurite will open based on certain stimuli (physical stimuli) • Different sensory neurosn respond to different stimuli Somatic Sensory Afferents Exhibit Distinct Functional Properties • Dermatome – territory innervated by each spinal nerve • Most of the info subserving touch is conveyed by slightly smaller diameter fibers and info about pain and temperature is conveyed by even smaller diameter fibers o The diameter of the axon determines the action potential conduction speed • Size of the receptive field – the area of the skin surface over which stimulation results in a significant change in the rate of action potentials o A given region of the body surface is served by sensory afferents that vary significantly in the size of their receptive fields • There are a lot of sensory neuritis closely packed in fingertips so will be able to detect small differences between two points, but not the same for neuritis in the back Somatic Sensory Afferents that Link Receptors to the CNS Sensory Function Receptor Type Afferent Axon Type Axon Diameter Conduction Velocity Proprioception Muscle spindle Decreases Decreases Touch Merkel, Meissner, Pacinian Cells Pain, temperature Free nerve endings Pain, temperature, Free nerve endings itch (unmyelinated) Mechanoreceptors Specialized to Receive Tactile Information • Four distinct classes of mechanoreceptive afferents that innervate the skin of the hand o Different endings, different response to stimulus, different recovery/length/intensity of stimulus • Merkel cell afferents – slowly adapting fibers; activate and deactivate very fast o Abundant in the fingertips o Excitable cells that express voltage-sensitive calcium channels and molecules that are required for synaptic vesicle release o Highest spatial resolution of all the sensory afferents  reading Braille • Meissner afferents – rapidly adapting fibers; stay activated longer Closest to the skin surface More than 4X as sensitive to skin deformation as Merkel afferents But their receptive fields are larger than Merkel afferents  transmit signals with reduced spatial resolution o Efficient in transducing info about the relatively low-frequency vibrations that occur when textured objects are moved across the skin o Info conveyed by Meissner afferents is responsible for detecting slippage between the skin and an object held in the hand • Pacinian afferents – rapidly adapting fibers o Located deep in the dermis o Looks like onion o Adapt more rapidly than Meissner corpuscles and have a lower response threshold o Very large receptive field (b/c so sensitive) o Detect vibrations transmitted through objects that contact the hand or being grasped by the hand • Ruffini afferents – on the periphery Mechanoreceptors Specialized for Proprioception • o o o