Stretching and squeezing of neuronal log firing rate distribution by psychedelic and intrinsic brain state transitions

Abstract

How psychedelic drugs change the activity of cortical neuronal populations and whether such changes are specific to transition into the psychedelic brain state or shared with other brain state transitions is not well understood. Here, we used Neuropixels probes to record from large populations of neurons in prefrontal cortex of mice given the psychedelic drug TCB-2. Drug ingestion significantly stretched the distribution of log firing rates of the population of recorded neurons. This phenomenon was previously observed across transitions between sleep and wakefulness, which suggested that stretching of the log-rate distribution can be triggered by different kinds of brain state transitions and prompted us to examine it in more detail. We found that modulation of the width of the log-rate distribution of a neuronal population occurred in multiple areas of the cortex and in the hippocampus even in awake drug-free mice, driven by intrinsic fluctuations in their arousal level. Arousal, however, did not explain the stretching of the log-rate distribution by TCB-2. In both psychedelic and naturally occurring brain state transitions, the stretching or squeezing of the log-rate distribution of an entire neuronal population reflected concomitant changes in two subpopulations, with one subpopulation undergoing a downregulation and often also stretching of its neurons' log-rate distribution, while the other subpopulation undergoes upregulation and often also a squeeze of its log-rate distribution. In both subpopulations, the stretching and squeezing were a signature of a greater relative impact of the brain state transition on the rates of the slow-firing neurons. These findings reveal a generic pattern of reorganisation of neuronal firing rates by different kinds of brain state transitions.

Logarithmically scaled, gamma distributed neuronal spiking

“…In agreement, the gamma PDF provides a better fit than the log‐normal one for the Neuropixels recordings of the multiple brain areas examined, as detailed in Dearnley et al. ( 2021 ). It is worth noting that we do not claim that gamma is ‘the right’ analytical distribution to use, but rather that it is relatively accurate and convenient to fit.…”

“…Often brain state transitions involve changes in the shape of the firing log‐rate distribution, which can get translated and squeezed or stretched. For example, the log‐rate distribution gets stretched upon transitions from non‐REM to REM sleep (Miyawaki et al., 2019 ; Mizuseki & Buzsaki, 2013 ; Watson et al., 2016 ) or from low to high level of arousal in the awake condition (Dearnley et al., 2021 ). Although the overall distribution of firing rates across the entire population changes across brain state transitions, the rank of individual neurons in the firing rate distribution remains (relatively) conserved, such that fast (slow) firing neurons in one state (e.g.…”

“…sleep) tend to maintain a high (low) rate in another (e.g. wakefulness) (Buzsaki & Mizuseki, 2014 ; Dearnley et al., 2021 ; Hengen et al., 2016 ; Watson et al., 2016 ). This is primarily attributed to stable GS rate across brain states, rather than the propensity of cells to enter AS modes (Levenstein et al., 2021 ).…”

Shared and Distinct Brain Regions Targeted for Immediate Early Gene Expression by Ketamine and Psilocybin

“…The therapeutic benefits of psychedelics are presumed to depend on neural plasticity. − Most recent research to study psychedelics-induced neural plasticity has focused on the neocortex and hippocampus. − However, as the compound is delivered systemically, many other regions in the brain can also potentially be responsive to psychedelic administration. Indeed, early work in rodents has shown strong responses to psychedelics in several subcortical nuclei.…”

Shared and distinct brain regions targeted for immediate early gene expression by ketamine and psilocybin

“…The therapeutic benefits of psychedelics are presumed to depend on neural plasticity (9)(10)(11). Most recent research to study psychedelics-induced neural plasticity has focused on the neocortex and hippocampus (12)(13)(14)(15)(16)(17)(18)(19). However, as the compound is delivered systemically, many other regions in the brain can also potentially be responsive to psychedelic administration.…”