Muscarinic receptor activation disrupts hippocampal sharp wave-ripples

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Cholinergic muscarinic innervations to the hippocampus play a role in learning and memory. Here we report that pharmacological activation of muscarinic receptors eliminates sharp wave-ripple events in the mouse hippocampal CA1 region in vivo and in vitro. This effect was associated with a decorrelation of excitatory synaptic inputs and a net increase in inhibitory conductances in pyramidal neurons. Multineuron calcium imaging revealed that muscarinic activation altered the spatiotemporal pattern of network activities. Thus, cholinergic input is likely to contribute to a neuromodulatory switch of hippocampal network states, as proposed in the “two-stage” model of learning processes.