Chapter 6: Neuronal Signaling and Structure of the Nervous System Central nervous system (CNS) brain + spinal cord

rd Peripheral nervous system (PNS) nerves that connect brain or spinal cord w/ muscles, glands, sense organs o Somatic single neuron btwn CNS s!eletal muscle cells" innervates s!eletal muscle" leads to muscle e#citation o $utonomic % neuron chain (connected by synapse) btwn CNS e&&ector organ" innervates smooth cardiac muscle, glands, '( neurons" can be e#citatory/inhibitory Neuron individual nerve cell" basic unit o& the nervous system" generates electrical signals releases neurotransmitters o Structure) Cell body (or soma) contains nucleus ribosomes" contains genetic in&o instructions &or protein synthesis *endrites highly branched outgrowth process" receive inputs &rom other neurons + branching , + cell sur&ace area , + capacity to receive signals $#on (or nerve &iber) long process that e#tends &rom the cell body" carries output to target cells (nitial segment (or a#on hilloc!) region where a#on connects to cell body" -trigger .one/ where electrical signals are generated 0ranching) o Collaterals branches o& a#ons o + branching a#ons or a#on collaterals , + cell1s sphere o& in&luence Sites &or releasing neurotransmitters) o $#on terminal releases neurotransmitters &rom the a#on o 2aricosities bulging areas along the a#on where some neurons release neurotransmitters 3yelin covers a#ons" layers o& highly modi&ied plasma membrane wrapped around the a#on by a nearby supporting cell" speeds up conduction o& electrical signals conserves energy o (n the brain spinal cord, the supporting cell is an oligodendrocyte o (n the PNS, Schwann cells &orm individual myelin sheaths at intervals Nodes o& 4anvier space btwn myelin that e#posed to e#tracellular &luid 3aintaining structure o $#onal movement movement o& organelles other materials btwn the cell body a#on terminals" depends on sca&&olding o& microtubule -motor proteins/ !inesin dynein 5inesin moves in anterograde (&rom the cell body toward a#on terminals)" move nutrient molecules, en.ymes, mitochondria, neurotransmitter vesicles, other organelles *ynein moves in retrograde (&rom the a#on terminal toward cell body)" carries recycles membrane vesicles, growth &actors, other chemical signals" also route by which harm&ul agents invade CNS o 6unctional classes Nerves groups o& a&&erent e&&erent neurons &ormed in the PNS $&&erent neurons convey in&o &rom the tissues/organs o& the body into CNS o Sensory receptors respond to physical/chemical changes in environment by generating electrical signals in neuron o 7ave only a single process, usually considered an a#on 8&&erent neurons convey in&o &rom CNS out to e&&ector cells (nterneurons connect neurons within CNS" 99: o& neurons are interneurons o ; o& interneurons assigned to a&&erent/e&&erent neurons varies on comple#ity o& the action they control Nerve &iber a single a#on Neurotransmitters chemical messengers that communicate w/ other cells" binds w/ speci&ic protein receptors on the membrane o& the receiving neuron o Synapse speciali.ed <unction btwn % neurons where one neuron alters the electrical chemical activity o& another Presynaptic neuron neuron conducting a signal towards a synapse

Postsynaptic neuron neuron conducting signals away &rom the synapse (ntegrators neurons serve as integrators since their output re&lects the balance o& inputs received by other neurons 'lial cells account &or 9=: o& cells in the CNS" surround the soma, a#on, dendrites" provide physical metabolic support o >ligodendrocyte &orms myelin covering in CNS o $strocyte regulate composition o& e#tracellular &luid in CNS by removing 5+ and neurotransmitters around synapses blood?brain barrier ? stimulate &ormation o& tight <unctions that ma!e up walls o& CNS capillaries sustain neurons metabolically (provides glucose, removes ammonia) guide neurons to ultimate destination stimulate neuronal growth by secreting growth &actors in&o@ signaling in the brain neuron?li!e characteristics ion channels receptors &or neurotransmitters en.ymes capability o& generating wea! electrical responses o microglia speciali.ed macrophage?li!e cell" per&orms immune &unction in CNS o ependymal line &luid?&illed cavities within brain spinal cord" regulate production/&low o& cerebrospinal &luid o Schwann cells (only in PNS) produce myelin sheath o& peripheral nerve &ibers Neural growth and regeneration o 'rowth) Stem cells (or precursor cells) go through cell division 8ach neuronal daughter cell di&&erentiates and migrates to its &inal location Processes sent out to become a#on dendrites 'rowth cone &orms tip o& each e#tending a#on" involved in &inding correct route &inal target &or the process $#on grows is guided by, usually glial cells, Cell adhesion molecules (reside on membranes o& glia embryonic neurons) neurotrophic &actors (growth &actors &or neural tissue) in&luence the route Aarget reached synapses &orm Synapses are active be&ore &inal maturation B early activity determines &inal &unction o *rugs, radiation, malnutrition, viruses cause permanent damage to &etal nervous system $poptosis programmed sel&?destruction o& neurons synapses" as many as C=?D=: degenerate 0elieved to re&ine or &ine?tune connectivity in nervous system *ivision o& neuron stem cells is complete be&ore birth o 4egeneration (& a#ons are severed, they can repair themselves as long as damage is not in CNS doesn1t a&&ect neuron cell bodies $#on segment separated degenerates causes a growth cone to grow o 4ate o& Emm/day Spinal in<ury usually crushes the tissue leaves a#ons intact $poptosis occurs in oligodendrocytes causing myelin coat to die a#ons cannot transmit e&&ectively 8#tracellular &luid is predominantly Na+ Cl? (ntracellular &luid is predominantly 5+, proteins,

non?di&&usible molecules

8lectrical potential (or potential di&&erence) separated electrical charges o& opposite sign that have potential to do wor! when brought together

o *etermined by di&&erence in amount o& charge btwn % points o Fnits , volts, usually millivolts Current movement o& electrical charge" caused by electrical potential btwn charges that are &lowing o 4esistance hindrance to electrical charge movement + resistance , G &low , called insulators G resistance , + rapid &low , called conductors >hm1s law) (( , current, 2 , voltage, 4 , resistance) e&&ects o& voltage resistance on current ( , 2/4 o Hipid layers o& plasma membrane have high electrical resistance 4esting membrane potential potential di&&erence across plasma membranes in resting cells, with the inside o& the cell negatively charged 3agnitude varies) ?C to ?E== m2" (n neurons, ?I= to ?9=m2 *epends on) o *i&&erences in speci&ic ion concentrations in intra/e#tracellular &luids o *i&&erences in membrane permeabilities to di&&erent ions o Stays the same unless there are changes in electrical current o Na 5 play most important roles, but chloride is a &actor in some cells Concentration di&&erences membrane potential in Na 5 are established by sodium?potassium pump that pumps Na out 5 in J Na+ out o& cell, % 5+ into cell o 8lectrogenic pump when a pump moves a net charge across the membrane directly contributes to membrane potential 3a<or &actor causing net movement o& ions across a membrane is electrical potential 8Kuilibrium potential membrane potential at which ions become eKual in magnitude but opposite in direction" no net movement o& ions o 3agnitude depends on concentration gradient &or that ion across the membrane + concentration gradient , + eKuilibrium potential o Nernst eKuation describes electrical potential necessary to balance a given ionic concentration gradient across a membrane so that the net &lu# o& the ion is = 8ion , eKuilibrium potential in m2, L , valence o& the ion, Co , e#tracellular concentration o& the ion, Ci , intracellular concentration o& the ion 8ion , ME log (Co) L (Ci) o 'oldman?7odg!in?5at. eKuation ('75) 5 has highest permeability Hea! potassium channels movement o& 5 out o& a cell down its concentration gradient so inside o& cell become negative Changes in *irection o& membrane potential >ccurs due to changes in permeability o& cell membrane to ions o 4esting , ?D=m2 , polari.ed (outside inside o& cell have di&&@ charges o *epolari.ation potential becomes less negative(closer to =) than the resting level o >vershoot reversal o& the membrane potential polarity" inside o& cell becomes positive relative to the outside o 4epolari.ation when a membrane potential returns toward resting value a&ter depolari.ation o 7yperpolari.ed potential is more negative than the resting level 'raded potential signals over short distances" magnitude o& potential change can vary o Named in relation to location o& the potential/&unction they per&orm (e#@ synaptic, receptor, pacema!er potential) o $ll cells are capable o& conducting graded potentials o Can occur in either a depolari.ing or hyperpolari.ing direction o 3agnitude is related to magnitude o& initiating event o *ecremental current &low o& charge decreases as distance &rom site o& origin increases o Summation additional stimuli can be added to depolari.ation &rom the E st stimulus

$ction potential long distance signaling o& nerve/muscle membranes" large alterations in membrane potential o 4apid can occur at high &reKuencies o Nerve/muscle cells, endocrine, immune, reproductive cells are capable o& producing action potentials 8#citable membranes ability to generate action potential is !nown as e#citability >nly e#citable membranes that can conduct action potentials Properties o& ion channels that allow &or changes in membrane potential o 2oltage?gated ion channels allow &or membrane to undergo action potentials Sodium channels &ast to respond to membrane voltage (nactivation gate limits &lu# o& sodium ions by bloc!ing channel shortly a&ter depolari.ation opens it Potassium channel slower to close 4esting membrane potential is closer to potassium eKuilibrium potential since there are more open 5 channels than Na channels o >ther channels) Higand?gated channels open in response to biding o& signaling molecules 3echanically gated channels open in response to physical de&ormation (stretching) o& plasma membrane $ction potential mechanism o *epolari.ing stimulus stimulates opening o& some voltage?gated Na channels $ction potentials occur ma#imally or not at all Ahreshold stimuli stimuli strong enough to depolari.e the membrane" about EC m2 less than resting potential Subthreshold potentials/stimuli wea! depolari.ations created no action potential generated o Na enters causing membrane depolari.ation o Ahreshold potential is reached depolari.ation becomes positive &eedbac! loop o *epolari.ation opens more Na channels until it overshoots so membrane becomes positive inside negative outside o (nactivation gates bloc! cycle o& positive &eedbac! by bloc!ing Na channels o 5 channels open slowly and 5 goes out o& cell causing repolari.ation o Na channels close o 7yperpolari.ation due to 5 channel closing slowly o 5 channels close due to induced negative &eedbac! process o 4esting membrane potential is restored 4e&ractory periods limit number o& action potentials an e#citable membrane can produce in a given time o $bsolute re&ractory period when an additional stimulus will not produce a % nd action potential during an action potential Na channels are either already open or have proceeded to inactivated state a&ter their E st action potential o 4elative re&ractory period a %nd action potential can be produced i& the stimulus strength is high Some but not all Na channels have returned to resting state some 5 channels are still open 0loc!ing action potentials o Prevented by local anesthetics such as procaine and lidocaine bloc!s Na channels $ction potential propagation seKuential opening/closing o& Na/5 channels along the membrane o 8ach action potential depends on positive &eedbac! cycle o 8#citable membranes can conduct action potentials in either direction, determine by stimulus location o 2elocity depends on &iber diameter i& &iber is myelinated + &iber diameter , + &aster action potential o Salutatory conduction $ction potentials only occur at nodes o& 4anvier" <ump &rom one node to the ne#t o *epolari.ation $&&erent neurons depolari.ation achieved by graded potential called receptor potential $ll other neurons depolari.ation due to graded potential &rom synaptic input called the synaptic potential or by spontaneous change in membrane potential called a pacema!er potential 8#citatory synapse brings membrane potential o& postsynaptic neuron closer to threshold

(nhibitory synapse membrane potential driven &arther &rom threshold or stabili.ed at its resting potential Convergence many synapses o& presynaptic cells a&&ecting one postsynaptic cell o $llows in&o &rom many sources to in&luence cell1s activity *ivergence ? single presynaptic cell a&&ects many postsynaptic cells o $llows E in&o source to a&&ect multiple pathways Aypes o& synapses o 8lectrical plasma membrane o& pre/post synaptic cells <oined by gap <unctions $llow local currents resulting &rom arriving action potentials to &low directly across the <unction though connecting channels &rom one neuron to another 8#tremely rapid Not commonly &ound in mammalian system o Chemical Structure) $#on o& presynaptic neuron ends in slight swelling Synaptic cle&t Postsynaptic density Cotransmitter addition neurotransmitter >perate in one direction 4elease o& Neurotransmitters o Neurotransmitters stored in small vesicles w/ lipid bilayer membranes 2esicles are doc!ed on presynaptic membrane at active .one by interaction o& group o& proteins(SN$48s soluble N?ethylmaleimide?sensitive &usion protein attachment protein receptors) o Neurotransmitters are released when action potential reaches terminal o& presynaptic membrane *epolari.ation causes calcium to activate processes by binding w/ synaptotagmins, leading to &usion o& doc!ed vesicles with the synaptic terminal membrane $ctivation o& postsynaptic cell o Neurotransmitters di&&use across the cle&t to receptors 4eceptor may be ionotropic(ion channels) or metabotropic(act indirectly on separate ion channels through a '?protein or %nd messenger) o Synaptic delay occurs btwn arrical o& action potential at presynatpic terminal membrane potential changes in postsynaptic cell o Fnbound neurotransmitters) 4eupta!e actively transported bac! into presynaptic a#on terminal or nearby glial cells *i&&use away &rom receptor site 8n.ymatically trans&ormed into inactive substances 8#citatory chemical synapses postsynaptic response is depolari.ation that brings membrane potential closer to threshold o 8PSP e#citatory postsynaptic potential" potential change to become slightly depolari.ed 'raded potential that spreads decrementally away &rom synapse by local current (nhibitory chemical synapses o (PSP inhibitory postsynaptic potential 7yperpolari.ing graded potential Hessens li!elihood that the postsynaptic cell will depolari.e to threshold and generate an action potential $ctivated receptors on postsynaptic membrane open Cl or 5 channels producing hyperpolari.ation $lso produced when there is increased H permeability in the postsynaptic cell Aemporal summation %nd synaptic potential adds to the previous one creates a greater depolari.ation" signal arrives &rom same presynaptic cell at di&&@ times Spatial summation % inputs occur at di&&@ location on same cell at same time

*i&&erent parts o& neuron have di&&erent thresholds o (nitial segment has low threshold than membrane o& cell body channels

dendrites due to high density o& voltage gated Na

Synaptic strength o Calcium concentration causes amount o& neurotransmitters released to vary every time it is activated o $#o?a#onic synapse a#on terminal o& one neuron end on a#on terminal o& another Neuron $ has no direct e&&ect on C, but has important in&luence on ability o& 0 to in&luence C Presynaptic inhibition presynaptic e&&ect decreases amount o& neurotransmitter released &rom 0 Presynaptic &acilitation presynaptic e&&ect increases amount o& neurotransmitter released &rom 0 Can alter calcium concentration pr e&&ect neurotransmitter synthesis o $utoreceptors neurotransmitters or other chemical messengers released by nearby neurons, glia, or the a#on terminal itsel&, that activates receptors on the presynaptic terminal Neuromodulators messengers that control the chemical messengers that elicit comple# responses o 8#@ hormones, paracrine agents, immune system messengers o $mpli&y or dampen e&&ectiveness o& ongoing synaptic acti&ity in postsynaptic cell o 4eceptors cause changes in metabolic processes (usually via ' proteins % nd?messengers)) that are slow Neurotransmitters o 4eceptors ? rapid communication o Aypes) $cetylcholine ? ma<or neurotransmitter in the PNS at the neuromuscular <unction and in the brain

Synthesi.ed &rom choline acetyl coen.yme $ in cytoplasm o& synaptic terminals o $cetylcholinesterase destroys $ch to release choline acetate Cholinergic neurons neurons releasing $ch Aype o& receptors) o nicotinic receptor respond to drug nicotine" contains ion channel permeable to both sodium potassium ions present in neuromuscular <unction o muscarinic receptor respond to mushroom poison muscarine" couple w/ ' proteins to alter activity o& di&&@ en.ymes ion channels o present at innervations o& glands, organs, heart

0iogenic amines small, charged molecules synthesi.ed &rom amino acids contain amino group (4? N7%) Catecholamines catechol ring(M?carbon ring w/ % hydro#yl groups)" &ormed &rom amino acid tyrosine converted to H?dopa bro!en down by 3$> o *opamine o Norepinephrine epinephrine $drenergic &ibers nerve &ibers releasing norephinephrine/epinephrine 3a<or classes $lpha?adrenergic receptors (NE, N%) 0eta?adrenergic receptors act via ' proteins to increase c$3P in postsynaptic cell (OE, O%, OJ) Serotonin produced &rom essential amino acid tryptophan" innervates every structure in the brain/spinal cord o 4egulate &ood inta!e, reproductive behavior, emotional states $mino acid neurotransmitters 'lutamate most common neurotransmitter at e#citatory synapses in the CNS o Hong?term potentiation (HAP) cellular process underlying learning memory $3P$ receptors &ound in postsynaptic membrane N3*$ receptors ? &ound in postsynaptic membrane 8#citoto#icity in<usry or death o& brain cells rapidly spreads

'$0$(gamma?aminobutyric acid) ma<or inhibitory neurotransmitter in the brain o Creates binding sites &or steroids, barbiturate, ethanal, ben.odia.epines 'lycine released &rom inbitory interneurons in spinal cord/brainstem" binds to ionotropic receptors on postsynaptic cells to allow Cl to enter to hyperpolari.e ro stabili.e membrane potential Neuropeptides % or more amino acids lin!ed by peptide bonds >thers gases that di&&use into intracellular &luid &rom nearby cells Nitric o#ide Carbon mono#ide