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SYNAPTIC PHYSIOLOGY

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Title: SYNAPTIC PHYSIOLOGY


1
SYNAPTIC PHYSIOLOGY
2
Student Preparation
  • Textbook of Medical Physiology, Guyton and Hall,
    Ch. 45
  • Neuroscience, Bear et al.,
  • Ch. 5, p. 38

3
Synapse - Definition
  • From the Greek word synapsis which means
    junction. The anatomical relation of one nerve
    cell to another cell which allows impulse
    transmission (information exchange) between
    neurons, or between neurons and muscle or glands.
    Term coined by Sir Charles Sherrington.

4
Synapses Can Be Classified By
  • Cytoarchitecture
  • Method of signal conduction (electrical/chemical)
  • Conductance of postsynaptic membrane to selective
    ion species (excitatory/inhibitory)

5
Classification of Synapses
  • Cytoarchitectural classification
  • Axo-dendritic synapse
  • Axo-somatic synapse
  • Axo-axonic synapse
  • Dendro-dendritic synapse
  • Soma-somatic synapse
  • Neuromuscular synapse (skel m. NM junction)
  • Neuroglandular synapse

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Classification of Synapses
  • Based on method of impulse conduction
    (electrical/chemical)
  • Electrical synapse (bridged or gap junction) -
    cytoplasmic continuity between pre- and
    postsynaptic elements allows direct conduction of
    electrical currents between cells by ion
    movements through connexons. Bidirectional.
  • Chemical synapse (unbridged junction) - thought
    to be the most numerous type of synapse. A
    chemical transmitter diffuses across a 20-30 nm
    synaptic cleft between cells. Unidirectional,
    with a delay of 0.3-5 msec.

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Classification of Synapses
  • Based on method of impulse conduction
    (electrical/chemical)
  • Electrical synapse (bridged or gap junction) -
    cytoplasmic continuity between pre- and
    postsynaptic elements allows direct conduction of
    electrical currents between cells by ion
    movements through connexons. Bidirectional.
  • Chemical synapse (unbridged junction) - thought
    to be the most numerous type of synapse. A
    chemical transmitter diffuses across a 20-30 nm
    synaptic cleft between cells. Unidirectional,
    with a delay of 0.3-5 msec.

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Classification of Synapses
  • Based on conductance of postsynaptic membrane to
    selective ion species (excitatory/inhibitory)
  • Excitatory synapse - an increase in postsynaptic
    membrane conductance to sodium, which depolarizes
    the membrane.
  • Inhibitory synapse - an increase in postsynaptic
    membrane conductance to potassium and/or chloride
    ions, which hyperpolarizes the membrane.

13
Excitatory post-synaptic potential
  • Action potential - Ca regulated release of
    neurotransmitter (NT) by synaptic vesicles
  • Attachment of NT to post-synaptic membrane
    receptors
  • Opening of ligand-gated channel to Na
  • Influx of Na makes the interior of the neuron
    more positive (excitatory post-synaptic
    potential, EPSP)
  • EPSP degrades with time and distance, moves
    toward neuron axon hillock

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EPSP
  • Superimposed EPSPs recorded from an a motor
    neuron (biceps-semitendinosus m.) in response to
    a repetitive shock to the afferent fibers of the
    Ia ending of its muscle spindle

16
Initiation of an action potential by an EPSP
  • If an EPSP reaches the axon hillock or a spike
    initiation zone, and is sufficiently large to
    exceed threshold, an action potential is produced

17
Spatial Summation of EPSPs
  • Subliminal volleys from two afferents applied to
    the same target neuron, closely spaced in time

18
Temporal Summation of EPSPs
  • Two well-spaced subliminal volleys to the same Ia
    fiber
  • Motor neuron response to same stimuli. Reduced
    interval EPSPs add up to produce an action
    potential

19
Spatial summation
Temporal summation
20
EPSP Summation
  • Both temporal and spatial summation occur to
    produce a depolarization at the axon hillock
    which may or may not trigger an action potential

21
Classification of Synapses
  • Based on conductance of postsynaptic membrane to
    selective ion species (excitatory/inhibitory)
  • Excitatory synapse - an increase in postsynaptic
    membrane conductance to sodium, which depolarizes
    the membrane.
  • Inhibitory synapse - an increase in postsynaptic
    membrane conductance to potassium and/or chloride
    ions, which hyperpolarizes the membrane.

22
Inhibitory post-synaptic potential
  • Action potential - Ca regulated release of
    inhibitory neurotransmitter (NT) by synaptic
    vesicles
  • Attachment of NT to post-synaptic membrane
    receptors
  • Opening of ligand-gated channel to Cl-/K
  • K efflux/Cl- influx to make the interior of the
    neuron more negative (inhibitory post-synaptic
    potential, IPSP)
  • IPSP degrades with time and distance, moves
    toward neuron axon hillock

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Inhibitory Post Synaptic Potential
  • IPSP recorded from an extensor motor neuron in
    response to stimulation of Ia fibers from the
    antagonistic flexor muscle

25
Temporal Summation of IPSPs
  • IPSPs sum when the interval between volleys is
    short
  • IPSPs reduce the membrane potential further below
    the critical firing level (threshold)

26
IPSPs and EPSPs sum algebraically
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Origin/Distribution of Molecules Necessary for
Synaptic Transmission
  • Molecules needed for synaptic transmission
    include enzymes, membrane constituents, and
    transmitter chemicals
  • Proteins are synthesized in the soma
  • Have to be transported down the axon
  • Metabolites must be transmitted back to the soma
    for elimination

30
Types of Axonal Transport
  1. Fast anterograde (orthograde) transport (400
    mm/day)
  • Vesicles, membranous organelles, certain
    neurotransmitters, enzymes, glycoproteins,
    precursors of receptors, lysosomes, mitochondria,
    growth factors

31
Types of Axonal Transport
  • 2. Axoplasmic flow (slow anterograde /orthograde)
    - 0.5-3 mm/day
  • 3. Axoplasmic flow (slow retrograde)- 5-10
    mm/day
  • Biosynthetic and other soluble enzymes,
    neurofilament proteins, tubulins (for
    microtubules)
  • breakdown products, actin, metabolic enzymes,
    viruses, tetnus toxoid, NGF, herpes, rabies

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Steps in Synaptic Transmission
  • Depolarization of presynaptic membrane
  • Opening of voltage-gated Ca2 channels
  • Ca2 influx causes fusion of vesicles with
    presynaptic membrane
  • Neurotransmitter diffuses into synaptic cleft
  • Neurotransmitter binds to receptors on
    post-synaptic and presynaptic membranes
  • Neurotransmitter action terminated by (1) enzyme
    action in the cleft, (2) diffusion, or (3)
    re-uptake into presynaptic terminal

34
Typical Transmitter ACh
  • First neurotransmitter identified, proving
    chemical neurotransmission
  • Otto Loewi (Austria, 1920s) studied
    innervation of the isolated frog heart by the
    vagus nerve
  • Experiment came to him in a dream twice
  • Vagal stimulation slowed the heart fluids
    bathing the first heart also slowed a second
    non-innervated heart
  • Vagusstoff later renamed acetylcholine
  • Serendipity seasonal variation in levels of AChE

35
Typical Transmitter ACh cont.
  • ACh is synthesized in the cytoplasm of the
    presynaptic terminal
  • Precursors choline and acetyl coenzyme A
  • Enzyme choline acetyltransferase (ChAT)
  • Quaternary amine charge limits crossing of
    membranes

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Typical Transmitter ACh cont.
  • ACh is stored in synaptic vesicles in the
    presynaptic terminal
  • Some vesicles are free-floating, others are
    anchored against the presynaptic membrane
  • Ca2 influx following depolarization causes
    vesicle fusion and NT release (in quanta) by
    exocytosis
  • Amount of NT released is proportional to amount
    of Ca2 influx

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  • Acetylcholine Metabolism

acetylcholine
ACh
choline acetate
esterase (AChE)
  • AChE is located in the synaptic cleft
  • Choline is taken back up into the
    presynaptic terminal active process
  • Acetate diffuses away to be utilized in
  • other metabolic roles

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Typical Transmitter ACh cont.
  • ACh is found in multiple locations
  • Motor neurons to skeletal muscle (NMJ)
  • Autonomic nervous system neurons (PSNS, SNS) to
    smooth muscle and glandular tissue
  • Central nervous system cortical arousal vs.
    sleep, Alzheimers disease, nicotine, etc.

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