期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 45, 期 12, 页码 1570-1585出版社
WILEY
DOI: 10.1111/ejn.13582
关键词
acetylcholine; gamma oscillations; hippocampus; muscarinic M1 receptors
资金
- Wellcome Trust Neural Dynamics PhD programme
- Wellcome Trust
- Wellcome Trust [101029/Z/13/Z] Funding Source: Wellcome Trust
- BBSRC [BB/N013956/1] Funding Source: UKRI
- EPSRC [EP/N014391/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/N013956/1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/N014391/1, 1280505] Funding Source: researchfish
- Wellcome Trust [101029/Z/13/Z] Funding Source: researchfish
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 suppresses 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 depolarisation, 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.
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