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
APStracts 3:0187N, 1996.
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
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