Characterize Htr1f function in the psilocybin response circuit

Characterize the function of the serotonin 1F receptor gene Htr1f in the mouse frontal-cortex circuit and determine whether the attention-identified late-phase reduction in Htr1f expression represents genuine psilocybin biology rather than a sequencing-platform artifact.

Background

Temporal attention analysis identifies Htr1f as a candidate gene with acute suppression after psilocybin and a possible second reduction at 72 hours. The late-phase signal is directionally consistent across most examined cell types but is not statistically significant in L2/3 IT neurons, where the sample size is small.

The interpretation is explicitly uncertain because baseline Htr1f expression differs between the SMART-Seq and MERFISH reference datasets, and the gene was excluded from a related figure because of this discrepancy. The paper also states that Htr1f's function in the relevant circuit is not well characterized, leaving both the biological role and the validity of the apparent sustained suppression unresolved.

References

First, the Allen Institute's SMART-Seq reference dataset shows substantial baseline Htr1f expression in mouse frontal cortex, but the newer MERFISH reference does not — a platform-dependent discrepancy serious enough that Htr1f was deliberately excluded from the corresponding figure in Liao et al.'s own preprint, and one that means the apparent 72h suppression could in part reflect a sequencing-method artifact rather than true biology. Second, Htr1f's function in this circuit is not well characterized in the literature.

— A Transformer-Based Delta Expression Encoder for Psilocybin Transcriptional Response: Architecture, Representations, and Biological Validation  (2609.08165 - Jayakumar, 8 Sep 2026) in Results, Section 6, paragraph discussing limitations of the Htr1f finding