Using Optogenetics to Shine a Light on the Motor-Cortical Embedding of the Mammalian “Psychedelic Signature Move”

Mice do not speak and cannot tell us about how they perceive the effects of psychedelic drugs. Behaviour at times speaks louder than words, though, and when taking a closer look at the animals’ behavioural response to LSD-type psychedelics, a distinctive “signature move” becomes evident. The psychedelic signature move is conserved across various mammals and characterised by a benign whole-body shake that is reminiscent of a dog shaking off water from its wet fur (therefore, the name “wet dog shake”). As wet dog shakes (like human psychedelia) are mediated by serotonin (5-HT) 2A receptors, they are often used as a behavioural proxy to study and learn about the mechanism of action of psychedelic drugs.

Despite more than half a century of research, however, methodological difficulties of neuro- and haemodynamic brain recordings in behaving animals have left us largely inconclusive about the neurophysiology of the given behaviour. In our study, we use highly refined techniques of optogenetic voltage imaging by selectively targeting the voltage-sensitive fluorescent protein “Butterfly 1.2” to supragranular cortical pyramidal cells. Our results reveal how the (movement-governing) motor-cortex orchestrates pyramidal-cellular and haemodynamic signals at the very instant at which mice engage in the psychedelic signature move.

Tobias Buchborn is a German Psychologist. In his diploma thesis he investigated the antidepressant-like properties of LSD in an animal model of depression. Tobias ran his PhD project in Neuroscience at the Institute of Pharmacology and Toxicology, Magdeburg, addressing differential tolerance to LSD and DMT and its relation to 5-HT2A-regulation. In 2016, Tobias was awarded an individual Marie Curie Research Fellowship and started to work in the Laboratory for Neuronal Circuit Dynamics, Imperial College London. Ever since, his research has been devoted to the pyramidal-cellular and blood-flow related corticodynamics of psychedelic drug action.