Spatial distribution and subunit composition of GABA(A) receptors in the inferior olivary nucleus

GABAergic inhibitory feedback from the cerebellum onto the inferior olivary (IO) nucleus plays an important role in olivo-cerebellar function. In this study we characterized the physiology, subunit composition, and spatial di stribution of gamma -aminobutyric acid-A (GABA(A)) receptors in the IO nucl eus. Using brain stem slices, we identified two types of IO neuron response to local pressure application of GABA, depending on the site of applicatio n: a slow desensitizing response at the soma and a fast desensitizing respo nse at the dendrites. The dendritic response had a more negative reversal p otential than did the somatic response, which confirmed their spatial origi n. Both responses showed voltage dependence characterized by an abrupt decr ease in conductance at negative potentials. Interestingly, this change in c onductance occurred in the range of potentials wherein subthreshold membran e potential oscillations usually occur in IO neurons. Immunostaining IO sec tions with antibodies for GABA(A) receptor subunits alpha1, alpha2, alpha3, alpha5, beta2/3, and gamma2 and against the postsynaptic anchoring protein gephyrin complemented the electrophysiological observation by showing a di fferential distribution of GABA(A) receptor subtypes in IO neurons. A recep tor complex containing alpha2 beta2/3 gamma2 subunits is clustered with gep hyrin at presumptive synaptic sites, predominantly on distal dendrites. In addition, diffuse alpha3, beta2/3, and gamma2 subunit staining on somata an d in the neuropil presumably represents extrasynaptic receptors. Combining electrophysiology with immunocytochemistry, we concluded that alpha2 beta2/ 3 gamma2 synaptic receptors generated the fast desensitizing (dendritic) re sponse at synaptic sites whereas the slow desensitizing (somatic) response was generated by extrasynaptic alpha3 beta2/3 gamma2 receptors.