Prefrontal cortex acetylcholine release, EEG slow waves, and spindles are modulated by M2 autoreceptors in C57BL/6J mouse

Recent evidence suggests that muscarinic cholinergic receptors of the M2 subtype serve as autoreceptors modulating acetylcholine (ACh) release in prefrontal cortex. The potential contribution of M2 autoreceptors to excitability control of prefrontal cortex has not been investigated. The present study tested the hypothesis that M2 autoreceptors contribute to activation of the cortical electroencephalogram (EEG) in C57BL/6J (B6) mouse. This hypothesis was evaluated using microdialysis delivery of the muscarinic antagonist AF-DX116 (3 nM) while simultaneously quantifying ACh release in prefrontal cortex, number of 7- to 14-Hz EEG spindles, and EEG power spectral density. Mean ACh release in prefrontal cortex was significantly increased (P < 0.0002) by AF-DX116. The number of 7- to 14-Hz EEG spindles caused by halothane anesthesia was significantly decreased (P < 0.0001) by dialysis delivery of AF-DX116 to prefrontal cortex. The cholinergically induced cortical activation was characterized by a significant (P < 0.05) decrease in slow-wave EEG power. Together, these neurochemical and EEG data support the conclusion that M2 autoreceptor enhancement of ACh release in prefrontal cortex activates EEG in contralateral prefrontal cortex of B6 mouse. EEG slow-wave activity varies across mouse strains, and the results encourage comparative phenotyping of cortical ACh release and EEG in additional mouse models.