THE REGULATION OF EXCITATORY INPUT TO INHIBITORY INTERNEURONS OF THE DENTATE GYRUS DURING HYPOXIA. DOHERTY, JAMES AND RAYMOND DINGLEDINE. Department of Pharmacology, Emory University Medical School, Atlanta, GA 30322.
APStracts 3:0187N, 1996.
ABSTRACT
The role of metabotropic glutamate (mGluR) and adenosine receptors in hypoxia- induced suppression of excitatory synaptic input to interneurons residing at the granule cell-hilus border in the dentate gyrus was investigated using whole-cell electrophysiological recording techniques in thin (250 (m) slices of immature rat hippocampus. Minimal stimulation evoked glutamatergic excitatory postsynaptic currents (EPSCs) in dentate interneurons in 68 + 4 % of trials during stimulation in the dentate granule cell layer (GCL) and 48 + 3 % of trials during stimulation in the CA3. Hypoxic episodes, produced by switching the perfusing solution from 95% O2/ 5% CO2 to a solution containing 95% N2/ 5% CO2 for 3-5 min., rapidly and reversibly decreased the synaptic reliability, or probability of evoking an EPSC, from either input without reducing EPSC amplitude, consistent with a presynaptic suppression of transmitter release. The mGluR antagonist (+)-a-methyl-4-carboxyphenylglycine ((+) MCPG, 500 (M) did not alter synaptic reliability or mean EPSC amplitude in either pathway. However, (+) MCPG significantly attenuated hypoxic suppression of input from both pathways, suggesting that mGluRs activated by release of glutamate partially mediate hypoxic suppression of EPSCs to dentate interneurons. The mGluR agonist, (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD; 100 (M) rapidly decreased the reliability of excitatory transmission from both the GCL (19 + 5 % of control) and CA3 (39 + 15 % of control). ACPD also increased the frequency of spontaneous EPSCs (sEPSCs) and evoked a slow inward current in dentate interneurons. Exogenous adenosine (10- 300 (M) decreased synaptic reliability for both pathways and reduced the frequency of sEPSCs, but did not cause a decrease in the mean amplitude of evoked EPSCs, consistent with a pre-synaptic suppression of excitatory input to dentate interneurons. Conversely, the selective adenosine A1 receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 200 nM-1 (M) and N6- cyclopentyl-9-methyladenine (N-0840, 1 (M) enhanced excitatory input to dentate interneurons by increasing the synaptic reliability for both the GCL and CA3 inputs. Adenosine A1 receptor antagonists did not, however, reduce hypoxic suppression of excitatory input to dentate interneurons. These results indicate that hypoxia induces a presynaptic inhibition of excitatory input to dentate interneurons mediated in part by activation of mGluRs, but not adenosine A1 receptors, whereas both mGluRs and adenosine A1 receptors can depress excitatory input to dentate interneurons during normoxic stimulation. Regulation of excitatory input to dentate interneurons provides a mechanism to shape excitatory input to the hippocampus under both normal and pathological conditions.

Received 5 June 1996; accepted in final form 3 September 1996.
APS Manuscript Number J455-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996