29.1.11 lecture 7. synapses, properties & transmission

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    Synapses, properties &

    Transmission

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    SYNAPSE

    Junction between 2 neurons:

    Axo-dendritic

    Axo-somaticAxo-axonal

    Resemble neuro-muscular junction.

    Between pre and post synaptic membranesynaptic cleft (20-30 nm wide).

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    A signal propagating down an axon to thecell body and dendrites of the next cell.

    NEURO-MUSCULAR JUNCTION

    http://upload.wikimedia.org/wikipedia/commons/3/3e/Neurons_big1.jpg
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    Synaptic Transmission Mechanism:

    electrical synapsesGap junctionsaretransmembrane protein pores between cells. Thepores represent a low electrical resistance. Mostelectrical synapsescontain many gap junctionsallowing free passage of ions and smallmolecules in both directions when open

    In some synapseselectrical transmissionpre & post synaptic membranes are very close

    gap junctionshighly permeable to ions

    rapid transmission of action potential.

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    Involves a chemical neuro-transmitter.Chemicaltransmission is more common. It resembles neuro-muscular transmission.

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    Nerve impulse comes from nerve terminaldepolarization of membrane of synaptic knob

    voltage gated Ca++channels open up in the

    membraneCa++ions move into synapticknobagitation of synaptic vesiclesvesiclesfuse with membrane of synaptic knobrelease

    of neuro-transmitter by exocytosis.

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    Depending on type of neurotransmitter& typeof change in permeability of post-synapticmembrane, post-synaptic neuron is either

    excited or inhibited. Neuro-transmitter binds with receptor on post-

    synaptic membraneopening of ion channelslocalized change in membrane potentialpost-synaptic membrane potential (PSP)2typesExcitatory (EPSP), Inhibitory (IPSP).

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    When EPSP is producedhypo-polarizationpotential becomes less negativereach threshold ofexcitation (-45mV)ACTION POTENTIAL in cellbody.

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    Purpose of EPSP:

    To bring potential of membrane to threshold

    (-45mV)

    It is gradedlike EPP (directly proportional toamount of neuro-transmitter released).

    There is no refractory period.

    Not self propagatinglike EPP.

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    IPSP:

    Inhibitory postsynaptic potential (IPSP) is atransient hyperpolarization of a neuron membrane. Thenegativity of the resting membrane potential increases(normally -70 mV) and summation of IPSPs may result

    in an effect Produced when post-synaptic neuron is inhibited. Neuro-transmitter is of inhibitory type (GABA.

    Glycine)

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    It binds with receptors on post-synaptic membranechange in permeability of membrane for K+or Cl-

    (there is opening ofK+or Cl- channelsefflux of K+cell becomes

    more negativehyper-polarization / IPSP.Opening of Cl- channelsextra-cellular Cl- moves

    into the cellmore negativehyper-polarization /IPSP.

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    Effect of IPSP:

    Because of IPSP, resting potential which is

    -65mV, becomes -70 to -75mVPost-synapticneuron is inhibitedPOST-SYNAPTIC

    INHIBITION.PRE-STNAPTIC INHIBITION:

    Synaptic knob has additional synapse with othernerve terminalsrelease of inhibitory neuro-

    transmitter from additional synapsesynaptic knob isinhibitedno further transmission from synapse nowto post-synaptic neuron.

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    EPSP Vs ACTION POTENTIAL:

    Property EPSP Action Potential

    Magnitude Low High

    Propagation &Duration

    Nil; it remainslocalized ( up to 20msec)

    Self propagating ( upto 2 msec)

    Refractory period absent present

    All or none law Not obeyed. It isgraded.

    obeyed

    Decrement (declineof size with distance)

    present Absent. Size isconstant

    Increasedpermeability to ions

    To Na+ & K+ atone time but Na+

    influx > K+ efflux

    Na+ first, then K+

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    EPP The neuromuscular endplateis the contact zone

    between the axons of motor neurons and striatedmuscle fibres

    It is a local potential of motor end plate, i-e., thethickened muscle membrane that is supplied by a

    motor-neuron, thus forming a component of neuro-muscular junction.

    Local potential recorded only at End plate region.

    It varies with strength of stimulus / amount ofneurotransmitter released. It can show summation.

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    Miniature End Plate Potentials (MEPPs)

    Miniature end plate potentials are the small (~0.5mV)depolarizations of the postsynaptic terminal caused bythe release of a single vesicle into the synaptic cleft.

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    EPP

    Because of EPPThreshold for actionpotential is reached (-65 mV).

    If RMP is -90 mV, then threshold is -65 mV, we

    need 25 mV potential change. Purpose of EPP is to reach the threshold of

    action potential.

    So voltage of EPP is much more than required,because required is only 25 mV.

    It is called SAFETY FACTOR.

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    EPP Vs APEPP Vs AP

    EPP:EPP:

    Local potential recorded onlyLocal potential recorded only

    at End plate region.at End plate region.

    Voltage: 0.5Voltage: 0.5

    mV (MEPP)mV (MEPP)

    EPP varies with strength ofEPP varies with strength of

    stimulus / amount ofstimulus / amount of

    neurotransmitter released.neurotransmitter released.

    Can show summation.Can show summation.

    AP:AP:

    SelfSelf--propagated.propagated.

    Voltage: 35Voltage: 35--40 mV40 mV

    AP follows All or NoneAP follows All or None

    Law/ requires only thresholdLaw/ requires only thresholdstimulus.stimulus.

    Does not show summation.Does not show summation.

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    Properties of Synaptic Transmission:

    DALES LAW:

    At a given synapse, only 1 type of neurotransmitter is released, it

    may be excitatory or inhibitory.

    Later on it was found that in certain cases release ofadditional substances at a given synapse

    e.g.,in noradrenergic synapses: along with nor-

    epinephrine, some dopamine, octopamine, dopamine-beta hydroxylase, neuropeptide Y & prostaglandins arealso released, although their role is ?? (not fully known)

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    LAW OF FORWARD CONDUCTION:

    Through synapses, impulses are conductedalways from pre-synaptic to post synapticneuron, never in backward direction.

    (NO REVERSE GEAR!!)

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    FATIGUE OF SYNAPTIC TRANSMISSION:

    If impulses are conducted through a synapse

    repeatedlyfatigue due to exhaustion of storesor progressive inactivation of receptorson post-synaptic membrane.

    Significance of fatigue????

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    pre- and postsynaptic sitesPresynaptic sites of NTF include: axonal branch pointconduction block; a failure of excitation-secretion coupling atthe presynaptic terminal; reductions in quantal release of ACh;

    and reductions in quantal size.Postsynaptic sites of NTF include: cholinergic receptordesensitization; and reduced sarcolemmal excitability.Susceptibility to NTF increases with stimulation frequency and ismost prevalent in fatigable fast-twitch motor units. In addition,susceptibility to NTF varies with age and with conditions ofaltered use

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    IN UNITY RESTS STRENGTH!

    SUMMATION:

    Adding up of effects of stimuli particularly if stimuli aresubthreshold.

    On a single motor neuron, thousands of synaptic knobsterminate to form synapses.

    About 80% of these synapses are on dendrites,remaining on cell body & few on axons.

    So single impulse coming to motor neuron through asynapse, cant excite a motor neuron &

    there must be summation of effects of stimuli.

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    POST-TETANIC FACILITATION

    OR POTENTIATION:

    (Rest is best for test!)

    If impulses are conducted through a synapse rapidlythen rest is given to synapsethen again impulses areconductedresponse of post-synaptic neuron is

    increased. Calcium ions enter in synaptic knob in each

    transmission, before fatigue occursincrease no. ofcalcium accumulate in knobmore neurotransmitter

    released

    more EPSP. After fatigueif rest is givenmore calcium ions

    become availablefacilitation.

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    ALKALOSIS INCREASE EXCITABILITY OF SYNAPSES,

    ACIDOSIS DEPRESSES SYNAPTIC TRANSMISSION:

    Increase excitability

    Caffeine(cerebral

    stimulantopen up

    open up) Theophylline

    Strychnine/ Kuchla

    (opisthotonus) Decreased calcium

    (tetany)

    Decrease excitability

    Anesthetics

    Hypoxia

    Increased calcium(stabilize)

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    Transmission of action potential

    along a nerve fiber:

    UNMYELINATED NERVE FIBER:

    Conductedpoint to point.

    A local circuit of current is formed between

    depolarized point and adjacent polarized point.Current flowing out through depolarized point

    activates sodium channels at polarized point

    depolarizationaction potentialthen a newcircuit of current is formed betweenthisdepolarized point and adjacent polarized point.

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    Incase of unmyelinatedfiberconductionvelocity is slowbecause it is point to point.

    Velocity: 2-5 m/sec

    Synapses only allow propagation between

    pre-synaptic to post-synaptic neuron inside thebody but in vitro, it is in both directions.

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    MYELINATED FIBERS:

    Node to node conduction.

    Saltatory / jumping conduction.

    All channels are present at nodes of Ranvier. Myelin sheath is absent and neurilemma is there at

    node.

    Velocity: 120 m/sec

    Thicker nerve fiber, longer internode, greater velocity.

    A alpha fibers.

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