SYNAPTIC PHYSIOLOGY

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SYNAPTIC PHYSIOLOGY
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Student Preparation

• Textbook of Medical Physiology, Guyton and Hall,
  Ch. 45
• Neuroscience, Bear et al.,
• Ch. 5, p. 38

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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.

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Synapses Can Be Classified By

• Cytoarchitecture
• Method of signal conduction (electrical/chemical)
• Conductance of postsynaptic membrane to selective
  ion species (excitatory/inhibitory)

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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.

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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

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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

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Spatial Summation of EPSPs

• Subliminal volleys from two afferents applied to
  the same target neuron, closely spaced in time

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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

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Spatial summation
Temporal summation
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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

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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.

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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

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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)

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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

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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

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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

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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

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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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