Y khoa, y dược - Fundamentals of the nervous system and nervous tissue: Part C

11 Fundamentals of the Nervous System and Nervous Tissue: Part CThe SynapseA junction that mediates information transfer from one neuron:To another neuron, orTo an effector cellThe SynapsePresynaptic neuron—conducts impulses toward the synapsePostsynaptic neuron—transmits impulses away from the synapsePLAYAnimation: SynapsesTypes of SynapsesAxodendritic—between the axon of one neuron and the dendrite of anotherAxosomatic—between the axon of one neuron and the soma of anotherLess common types:Axoaxonic (axon to axon)Dendrodendritic (dendrite to dendrite)Dendrosomatic (dendrite to soma)Figure 11.16DendritesCell bodyAxonAxodendriticsynapsesAxosomaticsynapsesCell body (soma) ofpostsynaptic neuron Axon(b)Axoaxonic synapsesAxosomaticsynapses(a)Electrical SynapsesLess common than chemical synapsesNeurons are electrically coupled (joined by gap junctions)Communication is very rapid, and may be unidirectional or bidirectionalAre important in:Embryonic nervous tissueSome brain regionsChemical SynapsesSpecialized for the release and reception of neurotransmittersTypically composed of two parts Axon terminal of the presynaptic neuron, which contains synaptic vesicles Receptor region on the postsynaptic neuronSynaptic CleftFluid-filled space separating the presynaptic and postsynaptic neuronsPrevents nerve impulses from directly passing from one neuron to the nextPLAYAnimation: NeurotransmittersSynaptic CleftTransmission across the synaptic cleft: Is a chemical event (as opposed to an electrical one)Involves release, diffusion, and binding of neurotransmittersEnsures unidirectional communication between neuronsInformation TransferAP arrives at axon terminal of the presynaptic neuron and opens voltage-gated Ca2+ channels Synaptotagmin protein binds Ca2+ and promotes fusion of synaptic vesicles with axon membraneExocytosis of neurotransmitter occursInformation TransferNeurotransmitter diffuses and binds to receptors (often chemically gated ion channels) on the postsynaptic neuronIon channels are opened, causing an excitatory or inhibitory event (graded potential)Figure 11.17 Action potentialarrives at axon terminal. Voltage-gated Ca2+channels open and Ca2+enters the axon terminal. Ca2+ entry causesneurotransmitter-containing synapticvesicles to release theircontents by exocytosis.Chemical synapsestransmit signals fromone neuron to anotherusing neurotransmitters.Ca2+SynapticvesiclesAxonterminalMitochondrionPostsynapticneuronPresynapticneuronPresynapticneuronSynapticcleftCa2+Ca2+Ca2+ Neurotransmitterdiffuses across the synapticcleft and binds to specificreceptors on thepostsynaptic membrane. Binding of neurotransmitteropens ion channels, resulting ingraded potentials. Neurotransmitter effects areterminated by reuptake throughtransport proteins, enzymaticdegradation, or diffusion awayfrom the synapse.Ion movementGraded potentialReuptakeEnzymaticdegradationDiffusion awayfrom synapsePostsynapticneuron123456Figure 11.17, step 1 Action potentialarrives at axon terminal.Chemical synapsestransmit signals fromone neuron to anotherusing neurotransmitters.Ca2+SynapticvesiclesAxonterminalMitochondrionPostsynapticneuronPresynapticneuronPresynapticneuronSynapticcleftCa2+Ca2+Ca2+Postsynapticneuron1Figure 11.17, step 2 Action potentialarrives at axon terminal. Voltage-gated Ca2+channels open and Ca2+enters the axon terminal.Chemical synapsestransmit signals fromone neuron to anotherusing neurotransmitters.Ca2+SynapticvesiclesAxonterminalMitochondrionPostsynapticneuronPresynapticneuronPresynapticneuronSynapticcleftCa2+Ca2+Ca2+Postsynapticneuron12Figure 11.17, step 3 Action potentialarrives at axon terminal. Voltage-gated Ca2+channels open and Ca2+enters the axon terminal. Ca2+ entry causesneurotransmitter-containing synapticvesicles to release theircontents by exocytosis.Chemical synapsestransmit signals fromone neuron to anotherusing neurotransmitters.Ca2+SynapticvesiclesAxonterminalMitochondrionPostsynapticneuronPresynapticneuronPresynapticneuronSynapticcleftCa2+Ca2+Ca2+Postsynapticneuron123Figure 11.17, step 4 Action potentialarrives at axon terminal. Voltage-gated Ca2+channels open and Ca2+enters the axon terminal. Ca2+ entry causesneurotransmitter-containing synapticvesicles to release theircontents by exocytosis.Chemical synapsestransmit signals fromone neuron to anotherusing neurotransmitters.Ca2+SynapticvesiclesAxonterminalMitochondrionPostsynapticneuronPresynapticneuronPresynapticneuronSynapticcleftCa2+Ca2+Ca2+ Neurotransmitterdiffuses across the synapticcleft and binds to specificreceptors on thepostsynaptic membrane.Postsynapticneuron1234Figure 11.17, step 5Ion movementGraded potential Binding of neurotransmitteropens ion channels, resulting ingraded potentials.5Figure 11.17, step 6ReuptakeEnzymaticdegradationDiffusion awayfrom synapse Neurotransmitter effects are terminatedby reuptake through transport proteins,enzymatic degradation, or diffusion awayfrom the synapse.6Figure 11.17 Action potentialarrives at axon terminal. Voltage-gated Ca2+channels open and Ca2+enters the axon terminal. Ca2+ entry causesneurotransmitter-containing synapticvesicles to release theircontents by exocytosis.Chemical synapsestransmit signals fromone neuron to anotherusing neurotransmitters.Ca2+SynapticvesiclesAxonterminalMitochondrionPostsynapticneuronPresynapticneuronPresynapticneuronSynapticcleftCa2+Ca2+Ca2+ Neurotransmitterdiffuses across the synapticcleft and binds to specificreceptors on thepostsynaptic membrane. Binding of neurotransmitteropens ion channels, resulting ingraded potentials. Neurotransmitter effects areterminated by reuptake throughtransport proteins, enzymaticdegradation, or diffusion awayfrom the synapse.Ion movementGraded potentialReuptakeEnzymaticdegradationDiffusion awayfrom synapsePostsynapticneuron123456Termination of Neurotransmitter EffectsWithin a few milliseconds, the neurotransmitter effect is terminatedDegradation by enzymesReuptake by astrocytes or axon terminal Diffusion away from the synaptic cleftSynaptic DelayNeurotransmitter must be released, diffuse across the synapse, and bind to receptorsSynaptic delay—time needed to do this (0.3–5.0 ms) Synaptic delay is the rate-limiting step of neural transmissionPostsynaptic PotentialsGraded potentialsStrength determined by:Amount of neurotransmitter releasedTime the neurotransmitter is in the area Types of postsynaptic potentials EPSP—excitatory postsynaptic potentials IPSP—inhibitory postsynaptic potentialsTable 11.2 (1 of 4)Table 11.2 (2 of 4)Table 11.2 (3 of 4)Table 11.2 (4 of 4)Excitatory Synapses and EPSPsNeurotransmitter binds to and opens chemically gated channels that allow simultaneous flow of Na+ and K+ in opposite directionsNa+ influx is greater that K+ efflux, causing a net depolarizationEPSP helps trigger AP at axon hillock if EPSP is of threshold strength and opens the voltage-gated channelsFigure 11.18aAn EPSP is a localdepolarization of the postsynaptic membranethat brings the neuroncloser to AP threshold. Neurotransmitter binding opens chemically gated ion channels, allowing the simultaneous pas-sage of Na+ and K+.Time (ms)(a) Excitatory postsynaptic potential (EPSP)ThresholdStimulusMembrane potential (mV)Inhibitory Synapses and IPSPsNeurotransmitter binds to and opens channels for K+ or Cl–Causes a hyperpolarization (the inner surface of membrane becomes more negative)Reduces the postsynaptic neuron’s ability to produce an action potentialFigure 11.18bAn IPSP is a localhyperpolarization of the postsynaptic membraneand drives the neuron away from AP threshold. Neurotransmitter binding opens K+ or Cl– channels.Time (ms)(b) Inhibitory postsynaptic potential (IPSP)ThresholdStimulusMembrane potential (mV)Integration: SummationA single EPSP cannot induce an action potential EPSPs can summate to reach thresholdIPSPs can also summate with EPSPs, canceling each other outIntegration: SummationTemporal summationOne or more presynaptic neurons transmit impulses in rapid-fire orderSpatial summationPostsynaptic neuron is stimulated by a large number of terminals at the same timeFigure 11.19a, bThreshold of axon ofpostsynaptic neuronExcitatory synapse 1 (E1)Excitatory synapse 2 (E2)Inhibitory synapse (I1)Resting potentialE1E1E1E1(a)No summation:2 stimuli separated in time cause EPSPs that do notadd together.(b) Temporal summation:2 excitatory stimuli closein time cause EPSPsthat add together.TimeTimeE1E1Figure 11.19c, dE1 + E2I1E1 + I1(d)Spatial summation ofEPSPs and IPSPs:Changes in membane potential can cancel each other out.(c) Spatial summation:2 simultaneous stimuli atdifferent locations causeEPSPs that add together.TimeTimeE1E2I1E1Integration: Synaptic PotentiationRepeated use increases the efficiency of neurotransmissionCa2+ concentration increases in presynaptic terminal and ostsynaptic neuronBrief high-frequency stimulation partially depolarizes the postsynaptic neuronChemically gated channels (NMDA receptors) allow Ca2+ entryCa2+ activates kinase enzymes that promote more effective responses to subsequent stimuliIntegration: Presynaptic InhibitionRelease of excitatory neurotransmitter by one neuron may be inhibited by the activity of another neuron via an axoaxonic synapseLess neurotransmitter is released and smaller EPSPs are formedNeurotransmittersMost neurons make two or more neurotransmitters, which are released at different stimulation frequencies50 or more neurotransmitters have been identifiedClassified by chemical structure and by functionChemical Classes of NeurotransmittersAcetylcholine (Ach)Released at neuromuscular junctions and some ANS neuronsSynthesized by enzyme choline acetyltransferaseDegraded by the enzyme acetylcholinesterase (AChE)Chemical Classes of Neurotransmitters Biogenic amines include:CatecholaminesDopamine, norepinephrine (NE), and epinephrineIndolaminesSerotonin and histamineBroadly distributed in the brainPlay roles in emotional behaviors and the biological clockChemical Classes of Neurotransmitters Amino acids include:GABA—Gamma ()-aminobutyric acid GlycineAspartateGlutamateChemical Classes of Neurotransmitters Peptides (neuropeptides) include:Substance PMediator of pain signalsEndorphinsAct as natural opiates; reduce pain perceptionGut-brain peptidesSomatostatin and cholecystokininChemical Classes of Neurotransmitters Purines such as ATP:Act in both the CNS and PNSProduce fast or slow responsesInduce Ca2+ influx in astrocytesProvoke pain sensationChemical Classes of Neurotransmitters Gases and lipidsNitric oxide (NO)Synthesized on demand Activates the intracellular receptor guanylyl cyclase to cyclic GMPInvolved in learning and memoryCarbon monoxide (CO) is a regulator of cGMP in the brainChemical Classes of Neurotransmitters Gases and lipidsEndocannabinoidsLipid soluble; synthesized on demand from membrane lipidsBind with G protein–coupled receptors in the brainInvolved in learning and memoryFunctional Classification of NeurotransmittersNeurotransmitter effects may be excitatory (depolarizing) and/or inhibitory (hyperpolarizing)Determined by the receptor type of the postsynaptic neuron GABA and glycine are usually inhibitoryGlutamate is usually excitatoryAcetylcholineExcitatory at neuromuscular junctions in skeletal muscleInhibitory in cardiac muscleNeurotransmitter ActionsDirect action Neurotransmitter binds to channel-linked receptor and opens ion channelsPromotes rapid responses Examples: ACh and amino acidsNeurotransmitter ActionsIndirect action Neurotransmitter binds to a G protein-linked receptor and acts through an intracellular second messengerPromotes long-lasting effectsExamples: biogenic amines, neuropeptides, and dissolved gasesNeurotransmitter ReceptorsTypesChannel-linked receptorsG protein-linked receptorsChannel-Linked (Ionotropic) ReceptorsLigand-gated ion channelsAction is immediate and briefExcitatory receptors are channels for small cationsNa+ influx contributes most to depolarizationInhibitory receptors allow Cl– influx or K+ efflux that causes hyperpolarizationFigure 11.20aIon flow blockedClosed ion channel(a) Channel-linked receptors open in response to binding of ligand (ACh in this case).Ions flowLigandOpen ion channelG Protein-Linked (Metabotropic) ReceptorsTransmembrane protein complexes Responses are indirect, slow, complex, and often prolonged and widespreadExamples: muscarinic ACh receptors and those that bind biogenic amines and neuropeptidesG Protein-Linked Receptors: MechanismNeurotransmitter binds to G protein–linked receptorG protein is activated Activated G protein controls production of second messengers, e.g., cyclic AMP, cyclic GMP, diacylglycerol or Ca2+G Protein-Linked Receptors: MechanismSecond messengersOpen or close ion channelsActivate kinase enzymesPhosphorylate channel proteins Activate genes and induce protein synthesisFigure 11.17b1 Neurotransmitter (1st messenger) binds and activates receptor.ReceptorG proteinClosed ionchannelAdenylate cyclaseOpen ion channel2 Receptoractivates G protein.3 G proteinactivates adenylate cyclase.4 Adenylate cyclase converts ATP to cAMP (2nd messenger). cAMP changes membrane permeability by opening or closing ion channels.5b cAMP activates enzymes.5c cAMP activates specific genes.Active enzymeGDP5a(b) G-protein linked receptors cause formation of an intracellular second messenger (cyclic AMP in this case) that brings about the cell’s response.NucleusFigure 11.17b, step 1(b) G-protein linked receptors cause formation of an intracellular second messenger (cyclic AMP in this case) that brings about the cell’s response.Receptor Neurotransmitter(1st messenger) bindsand activates receptor.1Figure 11.17b, step 2(b) G-protein linked receptors cause formation of an intracellular second messenger (cyclic AMP in this case) that brings about the cell’s response.ReceptorG proteinGTPGDPGTP Neurotransmitter(1st messenger) bindsand activates receptor. Receptoractivates Gprotein.Nucleus12Figure 11.17b, step 3(b) G-protein linked receptors cause formation of an intracellular second messenger (cyclic AMP in this case) that brings about the cell’s response.ReceptorG proteinAdenylate cyclaseGTPGDPGTPGTP Neurotransmitter(1st messenger) bindsand activates receptor. Receptoractivates Gprotein. G proteinactivatesadenylatecyclase.Nucleus123Figure 11.17b, step 4(b) G-protein linked receptors cause formation of an intracellular second messenger (cyclic AMP in this case) that brings about the cell’s response.ReceptorG proteinAdenylate cyclaseATPGTPGDPcAMPGTPGTP Neurotransmitter(1st messenger) bindsand activates receptor. Receptoractivates Gprotein. G proteinactivatesadenylatecyclase. Adenylatecyclase convertsATP to cAMP(2nd messenger).Nucleus1234Figure 11.17b, step 5a(b) G-protein linked receptors cause formation of an intracellular second messenger (cyclic AMP in this case) that brings about the cell’s response.ReceptorG proteinClosed ion channelAdenylate cyclaseOpen ion channelATPGTPGDPcAMPGTPGTP Neurotransmitter(1st messenger) bindsand activates receptor. Receptoractivates Gprotein. G proteinactivatesadenylatecyclase. Adenylatecyclase convertsATP to cAMP(2nd messenger). cAMP changesmembrane permeability byopening and closing ionchannels.Nucleus12345aFigure 11.17b, step 5b(b) G-protein linked receptors cause formation of an intracellular second messenger (cyclic AMP in this case) that brings about the cell’s response.ReceptorG proteinActive enzymeClosed ion channelAdenylate cyclaseOpen ion channelATPGTPGDPcAMPGTPGTP Neurotransmitter(1st messenger) bindsand activates receptor. Receptoractivates Gprotein. G proteinactivatesadenylatecyclase. Adenylatecyclase convertsATP to cAMP(2nd messenger). cAMP changesmembrane permeability byopening and closing ionchannels. cAMP activatesenzymes.Nucleus12345a5bFigure 11.17b, step 5c(b) G-protein linked receptors cause formation of an intracellular second messenger (cyclic AMP in this case) that brings about the cell’s response.ReceptorG proteinActive enzymeClosed ion channelAdenylate cyclaseOpen ion channelATPGTPGDPcAMPGTPGTP Neurotransmitter(1st messenger) bindsand activates receptor. Receptoractivates Gprotein. G proteinactivatesadenylatecyclase. Adenylatecyclase convertsATP to cAMP(2nd messenger). cAMP changesmembrane permeability byopening and closing ionchannels. cAMP activatesenzymes. cAMPactivatesspecific genes.Nucleus12345a5b5cNeural Integration: Neuronal PoolsFunctional groups of neurons that:Integrate incoming informationForward the processed information to other destinationsNeural Integration: Neuronal PoolsSimple neuronal poolSingle presynaptic fiber branches and synapses with several neurons in the poolDischarge zone—neurons most closely associated with the incoming fiberFacilitated zone—neurons farther away from incoming fiberFigure 11.21Presynaptic(input) fiberFacilitated zoneDischarge zoneFacilitated zoneTypes of Circuits in Neuronal Pools Diverging circuitOne incoming fiber stimulates an ever-increasing number of fibers, often amplifying circuitsMay affect a single pathway or severalCommon in both sensory and motor systemsFigure 11.22aFigure 11.22bTypes of Circuits in Neuronal Pools Converging circuitOpposite of diverging circuits, resulting in either strong stimulation or inhibitionAlso common in sensory and motor systemsFigure 11.22c, dTypes of Circuits in Neuronal PoolsReverberating (oscillating) circuitChain of neurons containing collateral synapses with previous neurons in the chainFigure 11.22eTypes of Circuits in Neuronal Pools Parallel after-discharge circuitIncoming fiber stimulates several neurons in parallel arrays to stimulate a common output cellFigure 11.22fPatterns of Neural ProcessingSerial processingInput travels along one pathway to a specific destinationWorks in an all-or-none manner to produce a specific responsePatterns of Neural ProcessingSerial processingExample: reflexes—rapid, automatic responses to stimuli that always cause the same responseReflex arcs (pathways) have five essential components: receptor, sensory neuron, CNS integration center, motor neuron, and effectorFigure 11.2312345Receptor Sensory neuronIntegration centerMotor neuronEffectorStimulusResponseSpinal cord (CNS)InterneuronPatterns of Neural ProcessingParallel processingInput travels along several pathwaysOne stimulus promotes numerous responsesImportant for higher-level mental functioningExample: a smell may remind one of the odor and associated experiencesDevelopmental Aspects of NeuronsThe nervous system originates from the neural tube and neural crest formed from ectodermThe neural tube becomes the CNSNeuroepithelial cells of the neural tube undergo differentiation to form cells needed for developmentCells (neuroblasts) become amitotic and migrateNeuroblasts sprout axons to connect with targets and become neuronsAxonal GrowthGrowth cone at tip of axon interacts with its environment via:Cell surface adhesion proteins (laminin, integrin, and nerve cell adhesion molecules or N-CAMs)Neurotropins that attract or repel the growth coneNerve growth factor (NGF), which keeps the neuroblast aliveAstrocytes provide physical support and cholesterol essential for construction of synapsesCell DeathAbout 2/3 of neurons die before birthDeath results in cells that fail to make functional synaptic contactsMany cells also die due to apoptosis (programmed cell death) during development