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 distribution of γ-aminobutyric acid-A (GABAA) receptors in the IO nucleus. Using brain stem slices, we identified two types of IO neuron response to local pressure application of GABA, depending on the site of application: a slow desensitizing response at the soma and a fast desensitizing response at the dendrites. The dendritic response had a more negative reversal potential than did the somatic response, which confirmed their spatial origin. Both responses showed voltage dependence characterized by an abrupt decrease in conductance at negative potentials. Interestingly, this change in conductance occurred in the range of potentials wherein subthreshold membrane potential oscillations usually occur in IO neurons. Immunostaining IO sections with antibodies for GABAA receptor subunits α1, α2, α3, α5, β2/3, and γ2 and against the postsynaptic anchoring protein gephyrin complemented the electrophysiological observation by showing a differential distribution of GABAA receptor subtypes in IO neurons. A receptor complex containing α2β2/3γ2 subunits is clustered with gephyrin at presumptive synaptic sites, predominantly on distal dendrites. In addition, diffuse α3, β2/3, and γ2 subunit staining on somata and in the neuropil presumably represents extrasynaptic receptors. Combining electrophysiology with immunocytochemistry, we concluded that α2β2/3γ2 synaptic receptors generated the fast desensitizing (dendritic) response at synaptic sites whereas the slow desensitizing (somatic) response was generated by extrasynaptic α3β2/3γ2 receptors.
Expression and Function of Estrogen Receptor Subtypes in Granulosa Cells: Regulation by Estradiol and Forskolin1