Glutamate receptor subunit GluA1 is necessary for long-term potentiation and synapse unsilencing, but not long-term depression in mouse hippocampus

Receptor subunit composition is believed to play a major role in the synaptic trafficking of AMPA receptors (AMPARs), and thus in activity-dependent synaptic plasticity. To isolate a physiological role of GluA1-containing AMPARs in area CA3 of the hippocampus, pair recordings were performed in organotypic hippocampal slices taken from genetically modified mice lacking the GluA1 subunit. We report here that long-term potentiation (LTP) is impaired not only at active but also at silent synapses when the GluA1 subunit is absent. The GluA1 knockout mice also exhibited reduced AMPAR-mediated evoked currents between pairs of CA3 pyramidal neurons under baseline conditions suggesting a significant role for GluA1-containing AMPARs in regulating basal synaptic transmission. In two independent measures, however, long-term depression (LTD) was unaffected in tissue from these mice. These data provide a further demonstration of the fundamental role that GluA1-containing AMPARs play in activity-dependent increases in synaptic strength but do not support a GluA1-dependent mechanism for reductions in synaptic strength.

► AMPA receptor subunit composition plays a major role in trafficking of those receptors in and out of the synaptic membrane and as a result, synaptic plasticity. ► We confirm that active excitatory synapses from hippocampus of a GluA1 AMPA receptor subunit null mouse, cannot undergo long-term potentiation, and show for the first time that silent synapses cannot be activated in this tissue as well. ► The amplitude of quantal excitatory postsynaptic currents is decreased in this knockout tissue. ► We also show for the first time that long-term depression is induced normally in this knockout tissue.