Acetylcholine modulates gamma frequency oscillations in the hippocampus by activation of muscarinic M1 receptors.

Author: Betterton RT1, Broad LM2, Tsaneva-Atanasova K3, Mellor JR1
1Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK.
2Eli Lilly & Company Ltd., Windlesham, Surrey, GU20 6PH, UK.
3Department of Mathematics, College of Engineering, Mathematics and Physical Sciences, University of Exeter, EX4 4QF, UK.
Conference/Journal: Eur J Neurosci.
Date published: 2017 Apr 12
Other: Special Notes: doi: 10.1111/ejn.13582. [Epub ahead of print] , Word Count: 239

Modulation of gamma oscillations is important for the processing of information and the disruption of gamma oscillations is a prominent feature of schizophrenia and Alzheimer's disease. Gamma oscillations are generated by the interaction of excitatory and inhibitory neurons where their precise frequency and amplitude are controlled by the balance of excitation and inhibition. Acetylcholine enhances the intrinsic excitability of pyramidal neurons and supresses both excitatory and inhibitory synaptic transmission but the net modulatory effect on gamma oscillations is not known. Here, we find that the power, but not frequency, of optogenetically-induced gamma oscillations in the CA3 region of mouse hippocampal slices is enhanced by low concentrations of the broad spectrum cholinergic agonist carbachol but reduced at higher concentrations. This bidirectional modulation of gamma oscillations is replicated within a mathematical model by neuronal depolarization, but not by reducing synaptic conductances, mimicking the effects of muscarinic M1 receptor activation. The predicted role for M1 receptors was supported experimentally; bidirectional modulation of gamma oscillations by acetylcholine was replicated by a selective M1 receptor agonist and prevented by genetic deletion of M1 receptors. These results reveal that acetylcholine release in CA3 of the hippocampus modulates gamma oscillation power but not frequency in a bidirectional and dose-dependent manner by acting primarily through muscarinic M1 receptors. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS: acetylcholine; gamma oscillations; hippocampus; muscarinic M1 receptors

PMID: 28406538 DOI: 10.1111/ejn.13582