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However, the continuous detection of cholinergic neurotransmission in selective brain regions in the mouse brain remains challenging and underexploited. Here, we have refined an established choline oxidase (ChOx) microelectrochemical biosensor and validated its use for long\u2010term recording in the freely moving mouse. Using a 75\u2010\u03bcm diameter polymer\u2010ChOx composite disc electrode, we have successfully monitored stable and reproducible chronic real\u2010time changes in choline\u2010induced amperometric currents in\u00a0vivo. Local infusions of choline and acetylcholine resulted in an increase in biosensor current in the hippocampus, while the inhibition of endogenous acetylcholinesterase (with neostigmine) significantly attenuated the response to exogenous acetylcholine. Systemic administration of donepezil produced a pronounced decrease in current in both the prefrontal cortex and hippocampus, with scopolamine and amphetamine resulting in signal increases that were not observed in animals with selective saporin lesioning (murine\u2010p75) of the cholinergic basal forebrain. Furthermore, continuous biosensor recording in both regions displayed diurnal oscillations across repetitive light\u2013dark phases. 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