The Journal of Neurophysiology Vol. 77 No. 1 January 1997, pp. 393-404
Copyright ©1997 The American Physiological Society

Regulation of Excitatory Input to Inhibitory Interneurons of the Dentate Gyrus During Hypoxia

James Doherty and Raymond Dingledine

Department of Pharmacology, Emory University Medical School, Atlanta, Georgia 30322

Doherty, J. and R. Dingledine. Regulation of excitatory input to inhibitory interneurons of the dentate gyrus during hypoxia. J. Neurophysiol. 77: 393-404, 1997. The role of metabotropic glutamate receptors (mGluRs) 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 with the use of whole cell electrophysiological recording techniques in thin (250 µm) slices of immature rat hippocampus. Minimal stimulation evoked glutamatergic excitatory postsynaptic currents (EPSCs) in dentate interneurons in 68 ± 4% (mean ± SE) of trials during stimulation in the dentate granule cell layer (GCL) and 48 ± 3% of trials during stimulation in 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 (+)--methyl-4-carboxyphenylglycine [(+)MCPG; 500 µM] 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 µM) 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 and evoked a slow inward current in dentate interneurons. Exogenous adenosine (10-300 µM) decreased synaptic reliability for both pathways and reduced the frequency of spontaneous EPSCs, but did not cause a decrease in the mean amplitude of evoked EPSCs, consistent with a presynaptic suppression of excitatory input to dentate interneurons. Conversely, the selective adenosine A₁ receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine (200 nM to 1 µM) and N⁶-cyclopentyl-9-methyladenine (1 µM) enhanced excitatory input to dentate interneurons by increasing 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.

This article has been cited by other articles:

				F. Laezza and R. Dingledine Voltage-Controlled Plasticity at GluR2-Deficient Synapses Onto Hippocampal Interneurons J Neurophysiol, December 1, 2004; 92(6): 3575 - 3581. [Abstract] [Full Text] [PDF]

				J. Doherty and R. Dingledine Reduced Excitatory Drive onto Interneurons in the Dentate Gyrus after Status Epilepticus J. Neurosci., March 15, 2001; 21(6): 2048 - 2057. [Abstract] [Full Text] [PDF]

				F. Laezza, J. J. Doherty, and R. Dingledine Long-Term Depression in Hippocampal Interneurons: Joint Requirement for Pre- and Postsynaptic Events Science, August 27, 1999; 285(5432): 1411 - 1414. [Abstract] [Full Text]

				J. Doherty and R. Dingledine Differential Regulation of Synaptic Inputs to Dentate Hilar Border Interneurons by Metabotropic Glutamate Receptors J Neurophysiol, June 1, 1998; 79(6): 2903 - 2910. [Abstract] [Full Text] [PDF]