Tobias Buchborn - Using optogenetics to shine a light on the mammalian “psychedelic signature move”

The psychedelic signature move, commonly known as head twitch response in rodents, serves as a central proxy for measuring serotonin 2A receptor activity in psychedelic research. Optogenetics and genetically encoded voltage imaging offer an alternative to traditional electrode-based measurements, allowing researchers to monitor neuronal and blood flow dynamics without surgical craniotomies. This methodology has revealed that head twitch behavior is embedded in specific mouse motor-cortical activation patterns, providing insights into the mechanisms underlying the drug-induced states. By utilizing intersectional genetic targeting, researchers can precisely express light-sensitive proteins in specific neuronal populations, such as layer 2/3 pyramid cells, and correlate their activation with physiological outcomes. This approach has demonstrated that cortical high-frequency oscillations are closely synchronized with the onset of the twitch itself, while low-frequency oscillations appear linked to broader limb movements. Moreover, observations indicate increased vasodilation in the brain stem around the time of the twitch, suggesting that blood flow modulation plays a critical role in mediating these behavioral responses.