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J Neurophysiol 85: 1686-1696, 2001;
0022-3077/01 $5.00
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The Journal of Neurophysiology Vol. 85 No. 4 April 2001, pp. 1686-1696
Copyright ©2001 by the American Physiological Society

Spatial Distribution and Subunit Composition of GABAA Receptors in the Inferior Olivary Nucleus

Anna Devor,1 Jean-Marc Fritschy,2 and Yosef Yarom1

 1Department of Neurobiology, Institute of Life Sciences, Hebrew University, Jerusalem 91904, Israel; and  2Institute of Pharmacology and Toxicology, University of Zurich, CH-8057 Zurich, Switzerland

Devor, Anna, Jean-Marc Fritschy, and Yosef Yarom. Spatial Distribution and Subunit Composition of GABAA Receptors in the Inferior Olivary Nucleus. J. Neurophysiol. 85: 1686-1696, 2001. 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 gamma -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 alpha 1, alpha 2, alpha 3, alpha 5, beta 2/3, and gamma 2 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 alpha 2beta 2/3gamma 2 subunits is clustered with gephyrin at presumptive synaptic sites, predominantly on distal dendrites. In addition, diffuse alpha 3, beta 2/3, and gamma 2 subunit staining on somata and in the neuropil presumably represents extrasynaptic receptors. Combining electrophysiology with immunocytochemistry, we concluded that alpha 2beta 2/3gamma 2 synaptic receptors generated the fast desensitizing (dendritic) response at synaptic sites whereas the slow desensitizing (somatic) response was generated by extrasynaptic alpha 3beta 2/3gamma 2 receptors.




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