Psilocybin biphasically modulates cortical and behavioral activity in mice
OpenAlex – January 20, 2024
Source: OpenAlex
Summary
Psilocybin, a serotonergic hallucinogen, dramatically reshapes how the brain processes sound. Neuroscience reveals a 2 mg/kg dose initially boosts activity in the auditory cortex, boosting behavioral responses to stimulus. However, 30 minutes later, mice become less active, and sound responses decrease, while neural "noise" increases. Intriguingly, neuronal selectivity for sounds remains stable. This work illuminates how psilocybin modulates intrinsic versus stimulus-driven activity in the sensory system, potentially explaining hallucinations without disrupting core perception, with implications for areas like the visual cortex and neurotransmitter receptor influence on behavior.
Abstract
SUMMARY Psilocybin is a serotonergic psychedelic believed to have therapeutic potential for neuropsychiatric conditions. Despite well-documented prevalence of perceptual alterations, hallucinations, and synesthesia associated with psychedelic experiences, little is known about how psilocybin affects sensory cortex or alters the activity of neurons in awake animals. To investigate, we conducted 2-photon imaging experiments in auditory cortex of awake mice and video analysis of mouse behavior, both at baseline and during psilocybin treatment. We found biphasic effects of psilocybin on behavioral and cortical activity. A 2 mg/kg dose of psilocybin initially increased behavioral activity and neural responses to sound. 30 minutes post-dose, mice became behaviorally hypoactive and cortical responses to sound decreased, while neural response variance and noise correlations increased. In contrast, neuronal selectivity for auditory stimuli remained stable during psilocybin treatment. Our results suggest that psilocybin modulates the role of intrinsic versus stimulus-driven activity in sensory cortex, while preserving fundamental sensory processing. Graphical Abstract. Summary of psilocybin’s effect on auditory cortical responses to sound in mice. 30 minutes after injecting the inert vehicle saline, typical auditory responses occur within a relatively narrow range of possible amplitudes, i.e., each neuron’s response variance is weakly correlated with a neighboring neuron’s response variance. In contrast, 30 minutes after injecting 2 mg/kg of psilocybin, population response variance becomes more correlated between individual neurons, and the range of response amplitudes increases. These findings suggest that psilocybin modulates the role of intrinsic versus stimulus-driven neural activity in sensory perception, which may serve as a basis for auditory hallucination at the level of neuronal micro-circuits.