Cortical Correlates of Psychedelic-Induced Shaking Behavior Revealed by Voltage Imaging

Tobias Buchborn*, Taylor Lyons, Chenchen Song, Amanda Feilding, Thomas Knöpfel

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review


(1) From mouse to man, shaking behavior (head twitches and/or wet dog shakes) is a reliable readout of psychedelic drug action. Shaking behavior like psychedelia is thought to be mediated by serotonin 2A receptors on cortical pyramidal cells. The involvement of pyramidal cells in psychedelic-induced shaking behavior remains hypothetical, though, as experimental in vivo evidence is limited. (2) Here, we use cell type-specific voltage imaging in awake mice to address this issue. We intersectionally express the genetically encoded voltage indicator VSFP Butterfly 1.2 in layer 2/3 pyramidal neurons. We simultaneously capture cortical hemodynamics and cell type-specific voltage activity while mice display psychedelic shaking behavior. (3) Shaking behavior is preceded by high-frequency oscillations and overlaps with low-frequency oscillations in the motor cortex. Oscillations spectrally mirror the rhythmics of shaking behavior and reflect layer 2/3 pyramidal cell activity complemented by hemodynamics. (4) Our results reveal a clear cortical fingerprint of serotonin-2A-receptor-mediated shaking behavior and open a promising methodological avenue relating a cross-mammalian psychedelic effect to cell-type specific brain dynamics.

Original languageEnglish
Article number9463
Number of pages15
JournalInternational Journal of Molecular Sciences
Issue number11
Early online date30 May 2023
Publication statusPublished - 1 Jun 2023

Scopus Subject Areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

User-Defined Keywords

  • voltage imaging
  • pyramidal cells
  • psychedelic
  • 5-HT2A receptor
  • wet dog shakes
  • hemodynamics
  • genetically encoded voltage indicator (GEVI)


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