The Journal of Neurophysiology Vol. 87 No. 1 January 2002, pp. 548-557
Copyright ©2002 by the American Physiological Society

7 Nicotinic Acetylcholine Receptors on GABAergic Interneurons Evoke Dendritic and Somatic Inhibition of Hippocampal Neurons

A. V. Buhler¹ and T. V. Dunwiddie^1,2,3,

 ¹Department of Pharmacology and  ²Neuroscience Program, University of Colorado Health Sciences Center, Denver 80262; and  ³Department of Veterans Affairs Medical Research Service, Denver, Colorado 80220

Buhler, A. V. and T. V. Dunwiddie. 7 Nicotinic Acetylcholine Receptors on GABAergic Interneurons Evoke Dendritic and Somatic Inhibition of Hippocampal Neurons. J. Neurophysiol. 87: 548-557, 2002. GABAergic interneurons in the hippocampus express high levels of 7 nicotinic acetylcholine receptors, but because of the diverse roles played by hippocampal interneurons, the impact of activation of these receptors on hippocampal output neurons (i.e., CA1 pyramidal cells) is unclear. Activation of hippocampal interneurons could directly inhibit pyramidal neuron activity but could also produce inhibition of other GABAergic cells leading to disinhibition of pyramidal cells. To characterize the inhibitory circuits activated by these receptors, exogenous acetylcholine was applied directly to CA1 interneurons in hippocampal slices, and the resulting postsynaptic responses were recorded from pyramidal neurons or interneurons. Inhibitory currents mediated by GABA_A receptors were observed in 27/131 interneuron/pyramidal cell pairs, but no instances of disinhibition of spontaneous inhibitory events or GABA_B receptor-mediated responses were observed. Two populations of bicuculline-sensitive GABA_A receptor-mediated currents could be distinguished based on their kinetics and amplitude. Anatomical reconstructions of the interneurons in a subset of connected pairs support the hypothesis that these two populations correspond to inhibitory synapses located either on the somata or dendrites of pyramidal cells. In 11 interneuron/interneuron cell pairs, one presynaptic neuron was observed that produced strong inhibitory currents in several nearby interneurons, suggesting that disinhibition of pyramidal neurons may also occur. All three types of inhibitory responses (somatic-pyramidal, dendritic-pyramidal, and interneuronal) were blocked by the 7 receptor-selective antagonist methyllycaconitine. These data suggest activation of these functionally distinct circuits by 7 receptors results in significant inhibition of both hippocampal pyramidal neurons as well as interneurons.