INTRODUCTION: Sleep deprivation can trigger psychosis-like states, including altered perception reflected in auditory hallucinations, however the underlying mechanisms are unclear. Dopaminergic signalling is disrupted after sleep deprivation and associated with psychosis.

AIM(S): We therefore aim to establish how sleep deprivation leads to psychosis-like perception, investigating striatal neuromodulatory signalling.

METHOD(S): To test this, we established a sleep-deprivation paradigm where mice are prevented from sleeping through motion. To establish whether this paradigm induced measurable effects on behaviour, we measured prepulse inhibition (PPI) and open-field locomotion. To specifically assess psychosis-like perception, we used a previously established task where mice detect tones and express confidence by waiting for reward. Hallucination-like percepts (HALIPs) are defined as high-confidence false alarms. To relate sleep deprivation to neuromodulatory state, we conducted mass spectrometry metabolic analysis in striatum and cerebrospinal fluid.

RESULTS: Sleep-deprived mice showed altered PPI and initial hyperlocomotion, validating our sleep-deprivation paradigm. Remarkably, sleep-deprived mice reported more HALIPs, demonstrating increased psychosis-like perception. Preliminary metabolomic profiling revealed significant alterations in neuromodulatory and related pathways.

CONCLUSIONS: Our results indicate that sleep deprivation induces behavioural alterations and psychosis-like perception and indicate a role of neuromodulatory state. Ongoing fibre photometry experiments aim to uncover the mechanisms directly linking neuromodulatory state to altered perception caused by sleep deprivation.