Input-dependent synaptic targeting of alpha(2)-subunit-containing GABA(A) receptors in synapses of hippocampal pyramidal cells of the rat.

Abstract

Pyramidal cells, expressing at least 14 subunits of the heteropentameric GABA(A) receptor, receive GABAergic input on their soma and proximal dendrites from basket cells, activating GABA(A) receptors and containing either parvalbumin or cholecystokinin and vasoactive intestinal polypeptide. The properties of GABA(A) receptors are determined by the subunit composition, and synaptic receptor content governs the effect of the presynaptic neuron. Using a quantitative electron microscopic immunogold technique, we tested whether the synapses formed by the two types of basket cell show a difference in the subunit composition of GABA(A) receptors. Terminals of one of the basket cells were identified by antibodies to parvalbumin. Synapses made by parvalbumin-negative terminals showed five times more immunoreactivity for the alpha(2) subunit than synapses made by parvalbumin-positive basket cells, whose synapses were frequently immunonegative. This difference is likely to be due to specific GABA(A) receptor alpha subunit composition, because neither synaptic size nor immunoreactivity for the beta(2/3) subunits, indicating total receptor content, was different in these two synapse populations. Synapses established by axo-axonic cells on axon initial segments showed an intermediate number of immunoparticles for the alpha(2) subunit compared to those made by basket cells but, due to their smaller size, the density of the alpha(2) subunit immunoreactivity was higher in synapses on the axon. Because the two basket cell types innervate the same domain of the pyramidal cell, the results indicate that pyramidal cells have mechanisms to target GABA(A) receptors, under presynaptic influence, preferentially to distinct synapses. The two basket cell types act via partially distinct GABA(A) receptor populations.