Neural control mechanisms involve neurons, which are the basic units that integrate and transmit electrical and chemical signals in the nervous system. Neurons have cell bodies that contain genetic material and protein synthesis machinery. They receive inputs via dendrites and transmit signals along axons via the release of neurotransmitters at synapses. Neural signals can be graded potentials that decay over short distances or action potentials that propagate long distances down axons. The initiation and propagation of action potentials relies on voltage-gated ion channels and the precise control of sodium, potassium, and other ion concentrations. Synapses allow neurons to communicate via the release of neurotransmitters that can have excitatory or inhibitory effects on the receiving neuron.

1. Neural Control Mechanisms Section AJohn Paul L. Oliveros, MD

2. Neural TissueNeuron: basic unit of the nervous systemServes as integratorsNeurotransmitters: chemical messengers released by nerve cellsParts:Cell bodyDendritesAxonAxon terminals

3. Neural TissueParts of a neuronCell BodyContains nucleus and ribosomesGenetic information and machinery for protein synthesisDendritesReceive inputs from other neuronsBranching increases the cell’s receptive surface areaAxonAKA nerve fiberSingle long process that extends from the cell body to its target cellsINITIAL SEGMENTAKA axon hillockPortion of axon closest to the cell body plus parts of the cell body“Trigger zone”CollateralsMain branches of the axonAxon TerminalEnding of each branch of axonReleases neurotransmittersVaricositiesBulging areas along the axonAlso releases neurotransmitters

4. Neural TissueMyelin SheathLayers of plasma membrane wrapped around the axon by a nearby supporting cellSpeeds up conduction of electrical signals along the axons and conserves energyOligodendroglia: CNSSchwann cells: PNSNodes of RanvierSpaces between adjacent sections of myelinAxons plasma is exposed to ECF

5. Neural TissueAxon TransportMovement of various organelles and materials from cell body to axon and its terminalTo maintain structure and function of the axonMicrotubulesRails along which transport occursLinking proteinsLink organelles and materials to microtubulesFunction as motors of axon transport and ATPase enzymesProvide energy from split ATP to the motorsAxon Terminalcell bodyOpposite route of transportRoute for growth factors and other chemical signals picked up at the terminalsRoute of tetanus toxins and polio and herpes virus

6. Neural Tissue

7. Neural TissuesynapseSpecialized junction between two neurons where one alters the activity of the otherPresynaptic neuronConducting signals toward a synapsePostsynaptic neuronConducts signals away from a synapse

8. Neural tissueGlial Cells/Neuroglia90% of cells in the CNSOccupy only 50% of CNSPhysically and metabolically support neuronsTypes:OligodendrogliaForm myelin covering of CNS axonsAstrogliaRegulate composition of ECF in the CNSRemove K+ ions and neurotransmitters around syapsesSustain neurons metabolically (provide glucose and remove ammonia)Embryo: guide neuron migration and stimulate neuron growthMany neuron like characteristicsMicrogliaPerform immune functions in te CNSSchwann cellsGlial cells of the PNSProduce myelin sheath of the peripheral nerve fibers

9. Neural Growth and degenerationEmbryo:Precursor cells: develop into neurons or glial cellsNeuron cell migrates to its final location and sends out processesGrowth cone: specialized tip of axons that finds the correct route and final target of the processesNeurotropic factors: growth factors for neural tissue in the ECF surrounding the growth cone or distant targetSynapses are then formed once target tissues are reachedNeural development occurs in all trimesters of pregnancy and upto infancy permanent damage by alcohol, drugs, radiation, malnutrition, and virusesFine tuning:Degeneration of neurons and synapses after growth and projection of axons50-70% of neurons die by apoptosisRefining of connectivity in the nervous system

10. Neural growth and regenerationNeuron damageOutside CNSDoes not affect cell bodySevered axon can repair itself and regain significant functionDistal axons degeneratesProximal axon develops growth cone and grows back to target organWithin CNSNo significant regeneration of the axon occurs at the damage siteNo significant return of function

11. Section BMembrane Potentials

12. Basic principles of electricityElectric potentialPotential of work obtained when separated electric charges of opposite signs are allowed to come together Potential differences/potentialDifference in the amount of charge between two pointsVolts: unit of electric potentialMillivolts: measurement in biological systemsCurrentMovement of electric chargeDepends on the potential differences between charges and the material on which they are movingResistanceHindrance to electric charge movementOhms law: I= E/RInsulatorMaterials with high electrical resistanceConductorMaterials with low electrical resistancee.g. water

13. Resting Membrane PotentialResting membrane potentialThe potential difference across the plasma membrane under resting conditionsInside cell: negative charge (-70mV)

14. Resting membrane potentialMagnitude of membrane potential is determined by:Differences of specific ion concentrations in the intracellular and extracellular fluidsDifferences in membrane permeabilities to the different ions

15. Resting membrane potentialEquilibrium potential: the membrane potential at which flux due to concentration gradient is equal to the flux due to electrical potential but at opposite directionsNo net movement of ion because opposing fluxes are equalMembrane potential will not undergo further changeIts value depends on the concentration gradient of an ion across the membrane

16. Resting membrane potential

17. Resting Membrane PotentialIn a resting cell, Na+ and K+ ion concentrations don’t change because the ions moved in and out by the Na+,K+-atpase pump equals that moved by the membrane channels electrical potential across membranes remain constantElectrogenic pumpPump that moves net charge across the membrane and contributes to the membrane potentialNa+,K+-ATPase pump:Sends out 3 Na+ ions for moving in 2K+ ionsMakes the inside of the cell more negative

18. Graded Potentials and Action PotentialsNerve cells transmit and process information through transient changes in the membrane potential from it s resting levelTwo forms of signalsGraded potentialOver short distancesAction potentialLong distance signalsDepolarizedPotential is less negative than the resting levelOvershootA reversal of the membrane potential polarityCell inside becomes positive relative to the outsideRepolarizeWhen the depolarized membranepotential returns toward the resting valuehyperpolarizeThe potential is more negative than the resting lavel

19. Graded potentialChanges in the membrane potential confined to a relatively small region of the plasma membraneDie out within 1-2 mm of siteProduced by a specific change in the cell’s environment acting on a specialized region of the membraneMagnitude of the potential change can varyLocal current is decrementalAmplitude decreases with increasing distance from the origin

20. Graded Potential

21. Graded Potential

22. Action PotentialsRapid and large alterations in the membrane potential 100mV from -70mV then reporalize to its resting membraneExcitable membranes: Plasma membranes capable of producing action potentialse.g. Neurons, muscle cells, endocrine cells, immune cells, reproductive cellsOnly cells in the body that can conduct action potentialsExcitability:Ability to generate action potentials

23. Ionic basis of action potentialsResting state:K+ and Cl- ion membranes openClose to K+ equilibriumDepolarizing phaseOpening of voltage-gated Na+ channels 100xMore + Na ions enter the cellMay overshoot: inside on the cell becomes positvely chargedShort duration of action potentialsResting membrane returns rapidly to resting potential becauseNa+ channels undergo inactivation near the peak of the action potential to then closeVoltage gated K+ channels begin to open

24. Ionic basis of action PotentialsAfterhyperpolarizationSmall hyperpolarization of the membrane potential beyond the resting levelSome of voltage gated K+ ions are still open after all Na+ have closedChloride permeability does’t change during action potentialThe amount of ions involve is extremely small and produces infinitesimal changes in the intracellular ion concentrationNa+,K+-ATPase pump makes sure that concentration gradient of each ions are restored to generate future action potentials

25. Mechanism of ion-channel changes1st part of depolarization: Due to local current opens up voltage gated channels sodium influx  increase in cell’s positive charge  increase depolarization (positive feedback)Delayed opening of K+ channelsInactivation of Na+ channels:Due to change in the conformation channel proteinsLocal anestheticse.g. Procaine, lidocaineBlock voltage gated Na+ channelsPrevent sensation of painAnimal toxins:Puffer fish: tetrodotoxinPrevent na+ component of action potentialIn some cells: Ca++ gates open prolonged action potential

26. Threshold and the all-or-none responseThe event that initiates the membrane depolarization provides an ionic current that adds positive charge to the inside of the cellEvents:K+ efflux increasesDue to weaker inside negativityNa+ influx increasesOpening of voltage gated channels by initial depolarizationAs depolarization increaes mor voltage gated channels openNa+influx eventually exceeds K+ efflux positive feedback starts action potentialThreshold potentialMembrane potential when the net movement of positive charge through ion channels is inwardAction potential only occurs after this is reachedAbout 15mV less negative than resting membrane potentialThreshold Stimuli strong enough to depolarize the membrane to threshold potentialSubthreshold potentialsWeak depolarizationsMembrane returnsto resting level as soon as stimuli is removedNo action potential generatedSubthreshold stimulusStimuli that causes subthreshold potentials

27. Threshold and the all-or-none responseStimuli with magnitude more than the threshold magnitude elicit action potentials with exactly the same amplitude with that of a threshold stimulusThreshold: membrane events not dependent on stimulus strengthDepolarization generates action potential because the positive feedback is operatingAll-or-none responseAction potentials occur maximally or they do not occur at allFiring of the gun analogy

28. Refractory periodsAbsolute refractory periodDuring action potential, a 2nd stimulus, no matter how strong, will not produce a 2nd action potentialNa+ channels undergo a closes and inactive state at the peak of the action potentialMembrane must be repolarized to return Na+ channels to a state which they can be opened againRelative refractory periodInterval followng the absolute refractory period during which a 2nd action potential can be producedStimulus must be greater than usual10-15ms longer in neuronsCoincides with the period of hyperpolarizationLingering inactivation of Na+ channels and increased number of K+ channels openAdditional action potentials firedDepolarization exceeds the increased thresholdDepolarization outlasr the refractory period

29. Action Potential PropagationThe difference in potentials betwen active and resting regions causes ions to flowLocal current depolarizes the membrane adjacent to the action potential site to its threshold potential producing another action potential action potential propagationGunpowder trail analogyAction potentials are not conducted decrementallyDirection of the propagation is away from a region of the membrane that has been recently activeDue to refractory period

30. Action potential propagationMuscle cellsAction potentials are initiated near the middle of these cylindrical cells and propagate towards the 2 endsNerve cellsInitiation at one end and propagate towards the other endVelocity of action potential propagation depends onFiber diameterThe larger, the fasterMyelinationMyelin is an insulatorAction potential only in the nodes of ranvierConcentration of Na+ channels is highSaltatory conduction/ jumping of action potentials from one node to the other as they propagate Faster conduction

31. Initiation of action potentialAfferent neuronsInitial depolarization threshold achieved by a graded potential (receptor potential) generated by sensory receptors at the peripheral endsEfferent neurons/ interneuronsDepolarization threshold due to either:1. Graded potential generated by synaptic input 2. Spontaneous change in the neurons membrane potential (pacemaker potential)Occurs in absence of external stimulie.g. Smooth muscle, cardiac musclesContnuous change in membrane permeability no stable resting membrane potentialImplicated in breathing, heart beat, GIT movements

33. Section CSynapses

34. SynapsesAnatomically specialized junction between 2 neuronsElectrical activity of a presynaptic neuron influences the elcetrical/metabolic activity of a postsynaptic neuron100 quadrillion synapses in the CNSExcitatory synapseMembrane potential of postsynaptic neurons is brought closer to the thresholdInhibitory synapsePostsynaptic neuron membrane potential is brought further away from the threshold or stabilizedConvergenceNeural input from many neurons affect one neuronDivergenceNeural input from one neuron affects many other neurons

35. Functional anatomy of synapses2 types of synapses:Electrical synapsesPre and postsynaptic cells joined by gap junctionsNumerous in cardiac and smooth muscle cellsRare in mammalian nervous systemChemical synapses Synaptic cleftSeparates pre and post synaptic neuronsPrevents direct propagation of electric currentSignals transmitted by means of neurotransmitterCo-transmittersAdditional neurotransmitter simultaneously released with another neurotransmitterSynaptic vesiclesStore neurotransmitter in the terminals

36. Functional anatomy of synapsesPresynaptic cell:Action potential axon terminal depolarization  voltage-gated Ca++ channels open Ca++ enters  fusion of synaptic vesicles to PM  release of transmitters by exocytosisPostsynaptic cell:Binding of neurotransmitters to receptors  opening or closing of specific ligand sensitive -ion channelsOne way conduction across synapses in generalBrief synaptic delay (0.2 sec) from action potential at presynaptic neuron to membrane potential changes in post synaptic cell

37. Functional anatomy of synapsesFate of unbound neurotransmittersAre actively transported back to the axon terminal/glial cellsDiffuse away from the receptor siteEnzymatically transformed into ineffective substances 2 kinds of chemical synapseExcitatoryResponse is depolarizationOpen postsynaptic-membrane ion channels permeable to positvely charged ionsExcitatatory postsynaptic potential (EPSP)Potential change wherien there is net movemnt of positively charge ions into the cell to slightly depolarize itGraded potential to bring the postsynaptic neuron closer to thresholdInhibitoryLessens likelihood for depolarization and action poterntialOpening of Cl- or sometimes K+ channelsInhibitory postsynaptic potential (IPSP)Hyperpolarizing graded potential

38. Activation of a postsynaptic cellIn most neurons, one excitatory synaptic event by itself is not enough to cause threshold to be reached in the postsynaptic neuronTemporal summation:Axon stimulated before the 1st EPSP has died awayThe 2nd EPSP adds to the previous one and creates a greater input than from 1 input aloneInput signals arrive at the same cell at different timesThe potentials summate because there is a greater number of open ion channelsSpatial summation:2 inputs occured at different locations on the same cell

39. Activation of a postsynaptic cell

40. Synaptic effectivenessA presynaptic terminal does not release a constant amount of neurotransmitters everytime it is activatedPresynaptic synapse (axon-axon synapse)Axon terminal of one ends on an axon terminal of another Effects:Presynaptic inhibitionDecrease the amount of neurotransmitter secreted Presynaptic facilitationIncrease the amount of neurotransmitter secreted

41. Modification of Synaptic transmission by Drugs and DiseaseAll synaptic mechanisms are vulnerable to drugsAgonist:Drugs that bind to a receptor and produces a response similar to normal activation of a receptorAntagonis:Drugs that bind to the receptor but aren’t able to activate itDiseases:Tetanus toxinProtease that destroys certain proteins in the synaptic-vesicle docking mechanism of inhibitory neurons to neurons supplying the skeletal muscleBotulinum toxin and spider venomAffect neurotransmitter release from synaptic vesiclesInterfere with docking proteinsAct on axons different from those acted upon by tetanus toxin

42. Synaptic effectiveness

43. Neurotransmitters and NeuromodulatorsNeuromodulatorsMessengers that cause complex responses/modulationAlter effectiveness of synapseModify postsynaptic cell’s response to neurotransmittersChange the presynaptic cell’s release, release, re-uptake, or metabolism of a transmitterReceptors for neuromodulators bring about changes in the metabolic processes in neurons via G-proteinsChanges occur within minutes, hours, or daysenzyme activityProtein synthesisAssociated with slower eventsLearning DevelopmentMotivational statesSensory/motor activities

44. Neurotransmitters and neuromodulatorsAcetylcholine (ACh)Synthesized from choline and acetyl coenzyme AReducing enzyme: acetylcholinesteraseMostly in the PNS, also in CNSNerve fibers: cholinergicReceptors: nicotinic, muscarinicFunction: attention, learning, memoryPathology: AlzheimersBiogenic aminesSynthesized from AA and contain an amino groupMC: dopamine, norepinphrine, serotonin, histamineEpinephrine: biogenic amine hormone secreted by adrenal medullaNorepinephrine: important neurotransmitter in CNS and PNS

45. Neurotransmitters and neuromodulatorsCatecholaminesDopamine, norepinephrine, epinephrineContain a catechol ring and an amine groupSynthesized from tyrosineReducing enzyme: Monoamine oxidase Catecholamine releasing neurons mostly in brainstem and hypothalamus but axons go to all parts of the CNSFunction: state of consciousness, mood, motivation, directed attention, movement, blood-pressure regulation, and hormone releaseCatecholaminesFibers: adrenergic, noradrenergicReceptors: Alpha, BetaFurther divide in Alpha1, alpha2, Beta1 and Beta2 receptors

46. Neurotransmitters and neuromodulators

47. Neurotransmitters and neuromodulatorsSerotoninBiogenic amine synthesized from trytophanEffects have slow onset and innervate virtually every structure of the brain and spinal cord.Has 16 different receptor typesFunction:Motor: excitatorySensation: inhibitoryLowest activity during sleep and highest during alert wakefulnessMotor activity, sleep, food intake, reproductive behavior, mood and anxietyPresent in non-neural cells (e.g. Platelets, GI tract, immune system)Amino Acid NeurotransmittersAmino acids that function as neurotransmittersMost prevalent neurotransmitter in the CNS and affect virtually all neurons thereExcitatory Amino Acids GlutamateAspartateFunction: learning, memory, neural developmentPathology: epilepsy, alzheimers, parkinsons disease,Neural damage after stroke, brain traumaDrugs: phencylidine (angel dust)Inhibitory Amino AcidsGABA (gamma-aminobutyric acid)GlycineDrugs: valium

48. Neurotransmitters and neuromodulatorsNeuropeptidesComposed of 2 or more AA linked together by peptide bondsFunction as hormones or paracrine agentsSynthesis: from large proteins produced by ribosomesFibers: peptidergicEndogenous opioidsB-endorphin, dynorphins, enkephalinsReceptors are site of action of opiate drugs (morphine, codeine)Function: analgesia, “jogger’s high”, eating and drinking behavior, CVS regulation, mood and behaviorSubstance PReleased by afferent neuronsRelay sensory information into the CNSNitric OxideDiffuse into the intracellular fluid of nearby cells from cells of originMessenger between neurons and effector cellsActivate cGMPFunction: learning, development, drug tolerance, penile erection, sensory and motor modulationATPVery fast acting excitatory transmitterAdenine

49. Section DStructure of the nervous system

50. Structure of the nervous systemDefinition of termsAxon/nerveLong extension from a single neuronNerveGroup of many nerve fibers that are travelling together to the same general location in the PNSPathway/tractA group of nerve fibers travelling together in the CNSCommisurePathway/tract that links the right and left halves the CNS2 types of pathways in the CNSLong neural pathwaysNeurons with long axons carry information directly between the brain and the spinal cord or between large regions of the brain Little opportunity for alteration in the information transmittedMultineural/multisynaptic pathwaysMade up of many neurons and many synaptic connectionsMany opportunities for neural processing along the pathwayGangliaGroup of neuron cell bodies in the PNSNucleiGroup of neuron cell bodies in the CNS

51. Structure of the nervous system

52. Spinal CordGray matterComposed of: interneuronscell bodies and dendrites of efferent neuronsentering fibers of afferent neuronsgangliaMore cells than myelinated fibersButterfly shaped and grayWhite matterGroups of myelinated axons of interneurons (fiber tracts / pathways)Dorsal rootWhere groups of afferent fibers from the PNS enter the SCDorsal root gangliaSmall bumps on the dorsal rootContain cell bodies of afferent neuronsVentral rootsWhere axons of the efferent nerves leave the SCSpinal nervesWhere the dorsal and ventral root combine a short distance from the SC31 pairs, divided into 4 levels (cervical, thoracic, lumbar, sacral)

53. Spinal Cord

54. Brain4 subdivisionsCerebrumDiencephalonBrainstemCerebellumForebrain: CerebrumDiencephalonBrainstem:MidbrainPonsMedulla oblongata

55. BrainCerebral ventricles4 interconnected cavitiesFilled with cerebrospinal fluid

56. Brain

57. Brain

58. Brain

59. Peripheral nervous systemConsists of 43 pairs of nervesEach nerve fiber is surrounded by a schwann cell that wrap some of the fibers with its membrane (myelin sheath)

60. Autonomic nervous systemEfferent innervation of all tissues other than skeletal muscleParallel chains, each with 2 neurons, connect the CNS and the effector cells

61. Autonomic nervous systemAnatomy of sympathetic nervous systemPreganglionic sympathetic fibers leave the spinal cord only between T1-L3Sympathetic trunks extend throughout the entire length of the spinal cord (cervical to sacral)Ganglia outside T1-L3 receive preganglionic fibers from the thoracolumbar regionPreganglionic fibers travel up or down for several segments before forming synapses with postganglionic neurons

62. Autonomic nervous systemNeurotransmittersAcetylcholineMajor neurotransmitter released between pre- and postganglionic fibers in the autonomic gangliaParasympatheticAcetylcholine: major neurotransmitter between postganglionic fibers and effector cellsSympatheticNorepinephrine: major neurotransmitter between postganglionic fibers and effector cells

63. Autonomic nervous system

64. Autonomic nervous systemThe heart, many glands, and smooth muscle cells have dual innervation (both sympathetic and parasympathetic)Usually the effect of sympathetic is the opposite of parasympathetic innervation in these tissuesThe activity of parasympathatetic and symphatetic is reciprocal with each otherFight-or-Flight responseFull response of the sympatheitic nervous systemIncrease response during physical or psychological stressAnimal is forced to challenge an attacker or run away from itHeart rate and BP increasesBlood flow to skeletal muscles, heart, and brain increasesLiver releases glucosePupils dilateBlood flow to GIT and skin decreased

65. Autonomic nervous system

66. Blood supply, blood brain barrier phenomenon, cerebrospinal fluid meningesProtect and support the CNSProduce, circulate and absorb CSF3 layersDura mater: next to the boneArachnoid: in betweenPia mater: next to nervous tissueCerebrospinal fluidFills the space between the arachnoid and the pia mater (subarachnoid)Hydrocephalus: flow of CSF is obstructed CSF accumulatesIncrease ventricular pressure compression of BV in brain  inadequate blood flow to neurons  neuronal damage and mental retardation

67. Blood supply, blood brain barrier phenomenon, cerebrospinal fluidGlucoseIn normal conditions, it is the only substrate metabolized by the brain to supply its energy requirementsStrokeNeuronal death due to stoppage of blood supply to a region of a brainBlood supply2% of body weightReceives 12-15% of total blood supplyHigh oxygen utilizationBlood-brain barrierComplex group of mechanisms that closely control both the kinds of substances that enter the extracellular fluid of the brain and the rates in which they enterMinimizes harmful substance that enter but reduces access of immune system to the brainMade up of cells that line up the smallest blood vessels of the brainLipid soluble substances enter the brain easilyNon-lipid soluble substances uses membrane transport proteinsChoroid plexusCells in the area secrete CSFResponsible for decreased K+ and Ca++ and increased Na+ and Cl- in CSF compared to plasmaTrap toxic heavy metals (e.g. lead)

68. The end