Review of Medical Physiology - William F. Ganong 2002

Physiology of Nerve and Muscle Cells
Synaptic and Junctional Transmission
Synaptic Transmission - Synaptic Plasticity and Learning

As a result of prior influences on the excitation arriving at a synapse, long-lasting functional changes can occur within it; that is, synaptic efficacy can be enhanced or diminished based on experience. Such changes are of considerable interest because they appear to underlie certain forms of Learning and Memory (see Chapter 16). Depending on their localization, these changes are classified as presynaptic or postsynaptic.

Posttetanic Potentiation

One form of plasticity is posttetanic potentiation, which is the enhancement of postsynaptic potentials in response to stimulation. This effect lasts up to 60 s and occurs following a brief period of tetanic stimulation of the presynaptic neuron. Tetanic stimulation causes an accumulation of Ca²⁺ in the presynaptic neuron to such an extent that the intracellular sites responsible for maintaining a low level of cytoplasmic Ca²⁺ become fully saturated.

Habituation

In the case of a low-intensity stimulus repeated over and over, the response to this stimulus gradually diminishes (habituation). This is caused by a decrease in the release of neurotransmitter from presynaptic terminals resulting from a reduction in intracellular Ca²⁺ due to the progressive inactivation of Ca²⁺ channels. This process can be short-lived or prolonged if such a low-intensity stimulus is applied repeatedly.

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Fig. 4-33. Generation and action of CO in vivo.

Sensitization

Sensitization consists of the appearance of prolonged, enhanced postsynaptic responses to a stimulus to which the animal has developed habituation, provided that the stimulus is paired one or more times with a noxious stimulus. At least in the marine slug Aplysia, the noxious stimulus triggers excitation in serotonergic Neurons that terminate on the presynaptic terminals of sensory neurons (see above).

Sensitization can occur as a temporary response or, if sustained by additional pairings of the noxious and initiating stimuli, exhibit The properties of short-term or long-term memory. Short-term sensitization is caused by a Ca²⁺-dependent change in adenylate cyclase activity, leading to increased cAMP production. In the case of long-term potentiation, stimulated processes include Protein Synthesis, growth, and an increase in the number of pre- and postsynaptic neurons and their interconnecting pathways involved in the process.

Long-Term Potentiation

Long-Term Potentiation (LTP) is a persistent, rapidly developing strengthening of postsynaptic potentials that occurs in response to presynaptic stimulation following a brief period of high-frequency stimulation of the presynaptic neuron. This phenomenon resembles posttetanic potentiation, but is much more prolonged and can last for days. Unlike posttetanic potentiation, long-term potentiation is triggered by an increase in intracellular Ca²⁺ concentration predominantly within the postsynaptic neuron rather than the presynaptic one. LTP occurs in many regions of The Nervous system, but it has been studied most thoroughly in the hippocampus. At Schaffer collateral synapses (dendrites of pyramidal Cells in the CA₁ region of the hippocampus), glutamate released from presynaptic terminals causes depolarization in postsynaptic neurons by acting primarily on AMPA receptors. This facilitates the relief of the magnesium block on NMDA receptors, allowing Ca²⁺ to enter the neuron along with Na⁺. The Ca²⁺ cation activates calmodulin, which in turn activates Ca²⁺/calmodulin-dependent protein kinase II. The kinase phosphorylates adjacent AMPA receptors, thereby increasing their conductance. Furthermore, it is likely that the Ca²⁺/calmodulin kinase somehow drives AMPA receptors to translocate to The Cell membrane within the synaptic cleft (Fig. 4-34). It is believed that a chemical signal travels from the postsynaptic neuron to the presynaptic one, triggering the long-term quantal release of glutamate in response to afferent stimulation. This signal is presumably arachidonic acid or NO, although the origin and even the existence of this retrograde signal remain incompletely understood.

The mechanism described above has been quite well elucidated for synapses on the dendrites of CA1 hippocampal neurons, but other mechanisms may also mediate long-term potentiation in other PARTS OF THE CNS. In this regard, It is interesting that when Ca²⁺ enters the postsynaptic neuron via AMPA receptors, an NMDA-independent long-term potentiation can occur in GABAergic neurons of the amygdala.

Long-Term Depression

Long-Term Depression (LTD) is the opposite phenomenon to long-term potentiation. In many respects, these phenomena are similar, but LTD is characterized by a decrease in synaptic efficacy. Long-term depression occurs in response to low-frequency stimulation of presynaptic neurons and is accompanied by a smaller increase in intracellular Ca²⁺ concentration than that seen in LTP. This is presumably caused by the dephosphorylation of AMPA receptors, a decrease in their conductance, and their lateral movement away from the synaptic region of The Plasma Membrane.