Nicotinic Receptors on Local Circuit Neurons in Dentate Gyrus: A Potential Role in Regulation of Granule Cell Excitability

• Published in: Journal of neurophysiology 2003-06, Vol.89 (6), p.3018-3028
• Main Authors: Frazier, Charles J, Strowbridge, Ben W, Papke, Roger L
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Acetylcholine - physiology; Afferent Pathways - physiology; Animals; Atropine - pharmacology; Choline - pharmacology; Dentate Gyrus - drug effects; Dentate Gyrus - physiology; Electrophysiology; Excitatory Amino Acid Antagonists - pharmacology; Glutamic Acid - physiology; Interneurons - physiology; Mossy Fibers, Hippocampal - physiology; Muscarinic Antagonists - pharmacology; Neural Inhibition; Neurons - drug effects; Neurons - physiology; Nicotinic Agonists - pharmacology; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Receptors, AMPA - antagonists & inhibitors; Receptors, AMPA - physiology; Receptors, GABA-A - physiology; Receptors, Kainic Acid - antagonists & inhibitors; Receptors, Kainic Acid - physiology; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - physiology; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - physiology; Synaptic Transmission
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.01036.2002

1 Department of Pharmacology and Therapeutics and 3 Department of Neuroscience, University of Florida, Gainesville, Florida 32610-0267; and 2 Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106 Submitted 15 November 2002; accepted in final form 5 February 2003 Although the dentate gyrus is one of the primary targets of septo-hippocampal cholinergic afferents, relatively little is known about the cholinergic physiology of neurons in the area. By combining whole cell patch-clamp recording with brief local application of exogenous agonists in horizontal slices, we found that there is robust expression of functional somatic 7-containing nicotinic acetylcholine receptors (nAChRs) on molecular layer interneurons, hilar interneurons, and the glutamatergic mossy cells of the dentate hilus. In contrast, the principal neurons of the dentate gyrus, the granule cells, are generally unresponsive to focal somatic or dendritic application of ACh in the presence of atropine. We also demonstrate that cholinergic activation of 7-containing nAChRs on the subgranular interneurons of the hilus can produce methyllycaconitine-sensitive GABAergic inhibitory postsynaptic currents (IPSCs) in nearby granule cells and enhance the amplitude of an electrically evoked monosynaptic IPSC. Further, activation of 7-containing nAChRs on subgranular interneurons that is timed to coincide with synaptic release of glutamate onto these cells will enhance the functional inhibition of granule cells. These findings suggest that a complex interplay between glutamatergic afferents from the entorhinal cortex and cholinergic afferents from the medial septum could be involved in the normal regulation of granule cell function. Such a relationship between these two afferent pathways could be highly relevant to the study of both age-related memory dysfunction and disorders involving regulation of excitability, such as temporal lobe epilepsy. Address for reprint requests: R. L. Papke, Dept. of Pharmacology and Therapeutics, University of Florida, P.O. Box 100267, HSC, Gainesville, FL 32610-0267 (E-mail: rpapke{at}college.med.ufl.edu ).