Psilocybin Attenuates Cortical Representations of Aversion in the Mouse Auditory Cortex

Area of Science:

• Neuroscience
• Pharmacology
• Psychiatry

Background:

• Psilocybin shows promise for treating affective and trauma-related disorders.
• The precise neural mechanisms, particularly how it alters sensory representations of learned emotional associations, are not well understood.

Purpose of the Study:

• To investigate how psilocybin modulates neural activity in the auditory cortex related to learned valence associations.
• To examine single-cell and population-level changes in response to auditory stimuli with associated emotional value.

Main Methods:

• Longitudinal two-photon calcium imaging was performed in awake C57BL/6 mice.
• Neural responses were recorded for tones, valenced stimuli, and tones previously associated with reward or aversion.
• Activity was analyzed at both single-neuron and population levels.

Main Results:

• Psilocybin selectively decreased neuronal responses to aversive stimuli and tones associated with prior aversion.
• Responses to reward-associated stimuli or newly formed aversive associations were not affected.
• Psilocybin acutely increased neural coordination, then selectively decreased it among neurons encoding aversive associations.

Conclusions:

• Psilocybin preferentially dampens consolidated aversive sensory representations in the auditory cortex.
• The drug does not broadly impair auditory processing or the formation of new aversive associations.
• Findings suggest a specific mechanism for psilocybin's therapeutic effects in emotional disorders.