BIO254:Silent

WIKIPEDIA BIO154/254: Molecular and Cellular Neurobiology

[Course Home] Wiki Home People Materials Schedule Help

Introduction

A silent synapse is a special type of excitatory glutamatergic synapse that relies on NMDA receptors to the exclusion of AMPA receptors. The voltage dependency of NMDA receptors causes them to act as logical AND gates, requiring both postsynaptic depolarization and glutamate binding to trigger an excitatory postsynaptic potential (EPSP).

The iGluR channel

Most excitatory synapses in the central nervous system are glutamatergic. In these synapses, glutamate released by the presynaptic cell acts on both metabotropic (mGluR) and ionotropic glutamate receptors (iGluR) in the postsynaptic membrane. Receptors in the iGluR channel can be classified as either NMDA (N-methyl-D-aspartate) or non-NMDA (kainate and AMPA).

Non-NMDA receptors contribute to the early phase of the excitatory postsynaptic current (EPSC) and generate peak current, whereas NMDA receptors contribute to the late phase as a slower component, as can be seen in the image below. This image also shows the effect of APV (see next section) on the EPSC:

NMDA receptors (NMDAR)

NMDA receptors additionally require postsynaptic depolarization to eject a Mg²⁺ ion that blocks the channel during normal operation. As a result, the relative contribution of NMDA receptors to the EPSC depends on the postsynaptic membrane potential.

Also unlike AMPA receptors, open NMDA receptors permit the influx of Ca²⁺, which plays a role in LTP (see below).

The inactivity of an NMDA-only synapse when the postsynaptic cell is polarized below -40 mV gives the silent synapse its name.

NMDA receptors are actively inhibited by APV (R-2-amino-5-phosphonopentanoate), which can thereby regulate silent synapse activity.

Long-term potentiation

Long-term potentiation (LTP) describes the process wherein the synaptic efficacy of two neurons is strengthened over time, in a way that depends on the simultaneity of firing (spike timing dependent plasticity). The best-studied form of this is hippocampal CA3-CA1 LTP, demonstrated by Timothy Bliss and Terje Lomo (1973). Brief high-frequency (tetanic) stimulation of a presynaptic cell can result in long-term enhancement of synaptic transmission. LTP additionally exhibits the following properties:

Cooperativity: The probability of inducing LTP increases with the number of stimulated afferents, and the strength of their stimulation. This reflects a postsynaptic depolarization threshold that must be exceeded in order to induce LTP.

Input specificity: LTP is restricted to the synapses that triggered the process, and does not propagate to nearby synapses.

Associativity: Weak stimulation on one pathway may be insufficient to induce LTP, though when coupled with strong stimulation on another, LTP can be induced on both pathways.

It was found that CA3-CA1 LTP requires both NMDAR and Ca²⁺, and involves depolarization of the postsynaptic cell, activation of NMDA receptors in that cell, the resulting influx of Ca²⁺, and the activation of secondary messengers by Ca²⁺.

The specific expression mechanisms of CA3-CA1 LTP are highly controversial. However, we do know that the expression of LTP is likely to involve both pre- and postsynaptic mechanisms, and that the probability of presynaptic neurotransmitter release is increased after LTP induction. At the postsynaptic cell, AMPA receptors are inserted into the cell membrane, which increases the conductance of the AMPA channel and thereby converts silent synapses into functional ones.

After the early phase of LTP (E-LTP) in which these pre- and post-synaptic changes occur, the late phase (L-LTP) can lead to the formation of new synapses.

Unlike CA3-CA1 LTP, mossy fiber LTP is not dependent on NMDAR, and might be expressed primarily by increased presynaptic neurotransmitter release.

Recent updates to the site

List of abbreviations: