Silent Synapse - Synaptic Transmission

Synaptic Transmission

Normal transmission across an excitatory synapse relies on the neurotransmitter glutamate, the glutamate-specific AMPA receptor (AMPAR), and calcium ions. Calcium ion entry into the presynaptic terminal causes the presynaptic release of glutamate which diffuses across the synaptic cleft binding to glutamate receptors on the postsynaptic membrane. There are four main types of glutamate receptors: AMPA receptors (AMPARs), NMDA receptors (NMDARs), Kainate receptors, and quisqualate receptors, some of which are also metabotropic receptors. Most research has been focused on the AMPARs and the NMDARs. When glutamate binds to AMPARs located on the postsynaptic membrane, they permit a mixed flow of Na+ and K+ to cross the cells membrane, causing a depolarization of the postsynaptic membrane. This depolarization is called the excitatory postsynaptic potential (EPSP).

Silent synapses release glutamate as do "normal" synapses, but they lack AMPARs on the surface membrane of the postsynapse. Only NMDARs (and perhaps metabotropic receptors) are found in the surface postsynaptic membrane where they can bind synaptically released glutamate. AMPARs are not completely absent from silent synapses, they are simply located inside the postsynaptic cell, where they cannot detect extracellular glutamate. The NMDAR is functionally similar to AMPAR except for two major differences: NMDARs carry ion currents composed of Na+, K+, but also (unlike most AMPAR) Ca2+; NMDARs also have a site inside their ion channel that binds magnesium ions (Mg2+). This magnesium binding site is physically located in the channel at a place within the electrical field generated by the membrane potential. Normally, current will not flow though the NMDAR channel, even when it has bound glutamate. This is because the ion channel associated with this receptor is plugged by magnesium, acting like a cork in a bottle. However, since the Mg2+ is charged and is bound within the membrane's electric field, depolarization of the membrane potential above threshold can dislodge the magnesium, allowing current flow through the NMDAR channel. This gives the NMDAR the property of being voltage-dependent, in that it requires strong postsynaptic depolarization to allow ion flux.