Synapic and Junctional Transmission


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All-or-none rule = Nerve impulses blew a certain voltage ( larger than -55mV) are ignored by the postsynaptic membrane.

Summation = All the action potentials received at the postsynaptic membrane are added together. This is called a summation of potentials. If the value of this summation is below the threshold potential (-55mV) the action potential is ignored.

Terminal Bouton = The end of a presynaptic axon is enlarged into a bouton.

Dendritic Spines = Projections of dendrites. Endings of presynaptic fibers in the cerebral and cerebellar cortices are commonly located on small knobs projecting from dendrites.
Sometimes, a presynaptic axon forms a net around the postsynaptic neuron (basket cells in cerebellum). In other cases, the presynaptic axons may interwine with the dendrites of the postsynaptic cell (climbing fibers of cerebellum).

SYNAPTIC ELEMENTS

chemical-synapse-fig-11-18
Synapse Size = 20 to 40 nm. Grey area = Postsynaptic Density, region with receptors, binding proteins and enzymes.

Within the presynaptic terminal

  • are many mitochondria, and
  • vesicles containing neurotransmitters

Synaptic vesicles are of three types:

  1. Vesicles that contain: Acetylcholine (ACh), Glycine, GABA, or Glutamate
  2. Vesicles that contain Cathecolamines
  3. Vesicles that contain Neuropeptides.

Neuropeptides (proteins) are synthesised in the neuronal body, and transported to the axonal ending by fast axoplasmic transport.
However, Type 1 and 2 vesicles recycle their neurotransmitters.

kiss-and-run discharge = vesicle fuses with presynaptic membrane and releases it’s contents to the outside. The presynaptic neuron performs exocytosis by kiss-and-run discharge at thickenings in the axonal membrane called active zones.
Active zones contain many Calcium (Ca2+ channels).

The Calcium that enters the presynaptic neuron triggers vesicle discharge within 200 microseconds.

Neurotransmitters must be released close to the postsynaptic membrane!
Neurexins on presynaptic membranes bind neurexin receptors on the postsynaptic membrane keeping it close. Different types of neuexins give synapses specificity.

fig-1-structure-of-the-trans-synaptic-neurexin-e-neuroligin-complex-the-putative

Several deadly toxins inhibit neurotransmission (zinc endopeptidases that cleave proteins involved in the exocytosis process). For instance, Tetanus and Botulinum.

CLINICAL:

Tetanus:

  • Released by Clostridium Tetani.
  • Binds irreversibly to the presynaptic membrane of the neuromuscular junction.
  • Travels via retrograde transport to the cell body, where it is picked by the terminals of presynaptic inhibitory interneurons (in the spinal cord)
  • Attaches to gangliosides and blocks release of glycine and GABA.
  • The activity of motor neurons is increased, resulting in:
  • spastic paralysis, “lockjaw” and involves spasms of the masseter.
  • Can be prevented by vaccination

Botulinum

  • Produced by Clostridium Botulinum
  • Prevents the release of ACh

ELECTRICAL EVENTS

Once an impulse reaches the presynaptic terminal, a response can be obtained in the postsynaptic delay. This delay represents the time needed to exocytose the synaptic mediators.

Excitatory Postsynaptic Potential (EPSP) = Postsynaptic membrane is more sensitive to other stimuli.
This happens when the postsynaptic membrane is partially depolarised by a stimuls, but not enough to cause an action potential throughout the postsynaptic axon. 0.5 ms postsynaptic delay, and 11.5 ms to reach the peak.
Multiple EPSP summate to trigger an action potential.

Similarly, there is an Inhibitory Postsynaptic Potential (IPSP), which represents a hyperpolarisation of the postsynaptic membrane.

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IPSP: When an inhibitory synaptic knob becomes active, the release of neurotransmitter triggers the opening of Chlorine channels. Cl- moves down the concentration gradient (from outside the cell to the inside). The net effect is transfer of charge, and increase in membrane potential ( more negative, and thus harder to depolarize).

Spatial and Temporal Summation = The location and time at which the summation takes place.

DENDRITIC SPINES and memory.

Spines allow for an interplay of inhibitory and excitatory activities of neurons, but not only.

Dendritic spines appear, change and even disappear over a time scale of minutes and hours. Protein synthesis occurs only in the soma, but pieces of mRNA migrate into the dendrites where they become associated with a single ribosome . This complex will continue to produce proteins which alter the effects of input from individual synapses, and confer the basis of motivation, learning, and long-term memory.

INHIBITION and FACILITATION as SYNAPSES

Inhibition can be

  • postsynaptic
  • presynaptic

– Postsynaptic inhibition occurs when an inhibitory transmitter is released from the presynaptic nerve terminal (E.g. Glycine, or GABA).

– Presynaptic inhibition – mediated by neurons whose terminals are on excitatory endings. This complex is called an axoaxonal synapse.
Three types of presynaptic inhibition have been described:

  1. Presynaptic receptors become activated to increase Cl- conductance. This decreases the size of action potentials reaching the excitatory ending
  2. Calcium entry is reduced, and consequently the amount of excitatory transmitter released. Voltage gated K+ channels are also opened, and the resulting K+ efflux also causes a decrease in Ca2+ influx.
  3. Direct inhibition of transmitter release independent of Ca2+.

– Presynaptic facilitation = Prolongation of an action potential. This is mediated by Serotonin, released at an axoaxonal synapse (cAMP increases,  K+ channels are phosphorylated – become closed)

Neurons may also inhibit themselves in a negative feedback manner.

Renshaw cell = A circuit in the spinal cord with 2 x Motor Neurons, and 1 x Inhibitory Interneuron. The first Motor neuron sends a collateral to the inhibitory interneuron, which terminates on the cell body of both motor neurons.
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A renshaw cell can be seen active in a reflex: Consider the Bicipital reflex. When triggered, a motor neuron (MI) becomes activated and contracts the flexors. MI sends a collateral to an inhibitory motorneuron which terminates on motor neurons that innervate the extensors. Those are inhibited to allow the flexion to happen.

 

 

 

 

 

 

 

NEUROMUSCULAR TRANSMISSION

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The axon terminals at a neuromuscular junction fit into junctional folds = depressions in the end plate. There is no convergence from multiple inputs (No summation takes place).

Neurotransmitter: ACh (Acetylcholine)
Receptors: Nicotinic Cholinergic Receptors
Number of receptors: 15-40 million.
ACh is removed by: Acetylcholinesterase

Series of events in summary:

  1. Motor neuron receives action potential
  2. Ca2+ entry via voltage-gated channels
  3. ACh release from presynaptic membrane
  4. Binding to receptors on postsynaptic membrane
  5. Na+ entry in the postsynaptic cell
  6. Local current between depolarised end-plate and adjacent muscle sarcoplasm
  7. Muscle fiber action potential initiation
  8. Propagated action potential travels to T-tubules
  9. ACh is degrated to prevent prolongued muscle contraction.

 

Miniature endplate potential = 0.5 mV – Produced by random release of small packets of ACh (quanta). The size of quanta varies directly with conc. of Ca2+ and indirectly with conc. with Mg2+ (Calcium causes spasms, Magnesium causes relaxation).

NERVE ENDINGS IN SMOOTH AND CARDIAC MUSCLE

Postganglionic nerve fibers that innervate smooth muscle show branches beaded with enlargements called varicosities – contain synaptic vesicles. Transmitters are liberated at each varicosity. This permits one neuron to innervate many effector cells.

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Neurotransmitter in Smooth Muscle: ACh, or Noradrenaline

Synapse en-passent = A varicosity forms a synapse (‘en-passent’, french for ‘on the move’) and then continues to give many more other synapses down the axon.

In the Heart

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Cholinergic and noradrenergic nerve fibers end on the SAN and AVN, and on the bundle of His.

Noradrenergic fibers also innervate ventricular muscle.

 

 

 

 

 

The nature of the potential (excitatory or inhibitory) does not depend on the transmitter but on the innervated structure.
There are two(2) types of potentials that can be elicited at a neuromotor juction:

  • Excitatory (Junction potential)
  • Inhibitory (Junction potential)

AXONAL INJURY AND DENERVATION SUPERSENSITIVITY

Orthograde Degradation or Wallerian Degradation occurs from the point of injury to the nerve terminal, interrupting neural transmission.

  • Cell membrane breaks down, followed by
  • Breakdown of myelin sheath.
  • Soma swells
  • Nucleus moves to the side, and
  • the Endoplasmatic Reticulum gets fragmented (Chromatolytic Reaction)

The nerve starts then to regrow, with multiple small branches projecting along the path the axon previously followed (regenerative sprouting). Sometimes the axons grow back to their original innervation, but most of the time they become tangled in the area of tissue damage.
This effect has been reduce by administering neurotrophins (molec. that promote neural growth)

Denervation hypersensitivity(or supersensitivity) = The muscle that has been denervated becomes extremely sensitive to ACh, as there is a marked increase of Nicotinic receptors.

SUMMARY:

Neuropeptides – Synthesised in Soma (Cell body) and transported to synapse.

Neurexins hold a synapse. Bind membranes of neurons

Signals at a postsynaptic membrane can be:

  • inhibitory (hyperpolarisation) or/and
  • excitatory (depolarisation)

Neurotransmitter at Motor-End plate: ACh (Acetylcholine)
Receptors: Nicotinic Cholinergic Receptors
Number of receptors: 15-40 million.
ACh is removed by: Acetylcholinesterase

Neurotransmitters in Smooth Muscle: ACh, or Noradrenaline

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