BIO254:Silent: Difference between revisions

Silent synapses are abundant in development and are found in several brain regions, including the hippocampus, the cerebral cortex, and the spinal cord. The "silence" of these synapses is the result of Mg++ blockade of NMDA receptors, which are voltage-dependent. Interestingly, glutamate released at silent synapses binds only to NMDA receptors, without binding to AMPA receptors. For years, this specificity has puzzles neurobiologists, but one explanation is that NMDA and AMPA receptors have significantly different affinities for binding the released glutamate neurotransmitter. The concentration of glutamate may be sufficient enough to activate NMDA receptors (high-affinity), but not the low-affinity AMPA receptors. A second possibility states that both AMPA and NMDA receptors exist on the postsynaptic terminal, but only the NMDA receptors are fully functional. Or, some specific excitatory synapses only have NMDA receptors; growing evidence tends to support this latter model. Immunocytochemical experiments perhaps provide the most compelling evidence for this explanation: staining done by Gomperts et al. (2000) shows that select excitatory synapses only possess NMDA receptors. These results support the first ("a") of two models for maturation of AMPA receptor signalling maturation recently reviewed by Groc et al. (2006) and shown in Figure 1 below:  

Figure 1. Maturing of AMPA receptor signalling according to two models. (a) Glutamate synapses start without AMPA receptors, but acquire them subsequently, through exposure to correlated activity at pre- and post-synapses, thereby becoming mature AMPA-signalling receptors. (b) A second model involves glutamate synapses starting with AMPA receptors and switching readily between AMPA-signalling and AMPA-silent states as a function of the synaptic activation history. Correlated activity at pre- and post-synapses converts the early synapse from this switching behavior to mature, stable AMPA-signalling.

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 (Figure 3).

Figure 3. AMPARs are inserted during LTP in hippocampal neurons in culture. Surface-expressed AMPARs on a living cultured hippocampal neuron detected using antibodies before (top, orange) and after (middle, purple) induction of NMDAR-dependent LTP in culture. Colocalization is shown in the bottom panel. (Isaac, 2003)

Isaac, JTR. (2003) Postsynaptic silent synapses: evidence and mechanisms. Neuropharmacology: 45: 450-460.