Differential localization of GABAA receptor subunits in relation to rat striatopallidal and pallidopallidal synapses

As a central integrator of basal ganglia function, the external segment of the globus pallidus (GP) plays a critical role in the control of voluntary movement. The GP is composed of a network of inhibitory GABA-containing projection neurons which receive GABAergic input from axons of the striatum (Str) and local collaterals of GP neurons. Here, using electrophysiological techniques and immunofluorescent labeling we have investigated the differential cellular distribution of alpha 1, alpha 2 and alpha 3 GABA(A) receptor subunits in relation to striatopallidal (Str-GP) and pallidopallidal (GP-GP) synapses. Electrophysiological investigations showed that zolpidem (100 nm; selective for the alpha 1 subunit) increased the amplitude and the decay time of both Str-GP and GP-GP IPSCs, indicating the presence of the alpha 1 subunits at both synapses. However, the application of drugs selective for the alpha 2, alpha 3 and alpha 5 subunits (zolpidem at 400 nm, L-838,417 and TP003) revealed differential effects on amplitude and decay time of IPSCs, suggesting the nonuniform distribution of non-alpha 1 subunits. Immunofluorescence revealed widespread distribution of the alpha 1 subunit at both soma and dendrites, while double- and triple-immunofluorescent labeling for parvalbumin, enkephalin, gephyrin and the gamma 2 subunit indicated strong immunoreactivity for GABA(A)alpha 3 subunits in perisomatic synapses, a region mainly targeted by local axon collaterals. In contrast, immunoreactivity for synaptic GABA(A)alpha 2 subunits was observed in dendritic compartments where striatal synapses are preferentially located. Due to the kinetic properties which each GABA(A)alpha subunit confers, this distribution is likely to contribute differentially to both physiological and pathological patterns of activity.