Biology subjects

Knox, C. A.

Publications and source records attributed to Knox, C. A..

5 recordsLinked to original sources

bioRxiv2026

Psychedelic drug action at dendrites is gated by behavioral state and serotonin receptors

How psychedelics act on cortical dendrites to produce long-lasting structural plasticity remains poorly understood. Here, we characterize the effects of psilocybin on dendritic calcium dynamics in pyramidal tract neurons of the mouse medial frontal cortex. Psilocybin transiently increases calcium event rates in apical dendritic tufts over a time course that parallels the drugs pharmacokinetics in the brain. This acute effect is brain state-dependent, occurring selectively during quiet wakefulness, and was abolished by cell type-specific deletion of the 5-HT2A receptor. Under control conditions, dendritic calcium signaling predicts subsequent spine formation, but this relationship is not preserved following psilocybin administration. Together, these findings reveal that psilocybin engages brain state- and 5-HT2A receptor-dependent dendritic signaling, while altering the relationship between acute dendritic activity and long-term structural plasticity. The results suggest that the mechanisms linking acute dendritic signaling to structural remodeling differ between physiological and psychedelic-induced plasticity.

neuroscience↗

bioRxiv2026

Structural plasticity and enhanced fear extinction following psilocybin in chronically stressed mice

The classic psychedelic psilocybin elicits long-lasting neural plasticity and behavioral effects, but prior studies largely examined stress-naive animals. Using longitudinal imaging, we show that psilocybin increases dendritic spine density in frontal cortical neurons and facilitates fear extinction after chronic restraint stress, demonstrating psilocybins effects in a translationally relevant mouse model.

neuroscience↗

bioRxiv2026

Psilocybin reshapes cortical inhibition through selective interneuron recruitment

Psychedelics show therapeutic potential for treating psychiatric disorders. While studies have emphasized the roles of cortical pyramidal cells, GABAergic neurons also express serotonin receptors and are therefore likely targets of psychedelics. In this study, we determine the effect of psilocybin on the activity dynamics of major GABAergic cell types in the mouse medial frontal cortex. Psilocybin reduces the firing of somatostatin-expressing interneurons, but increases the activity of parvalbumin-expressing interneurons. This cell type-specific response is unlikely to involve vasoactive intestinal peptide-expressing interneurons. Instead, pharmacological blockade and conditional knockout experiments demonstrate that psilocybin acts on the 5-HT1A receptor at SST interneurons, which contributes to the drugs long-term behavioral effects. Collectively, the results reveal that the classic psychedelic psilocybin alters cortical inhibition in a cell type-specific manner.

neuroscience↗

bioRxiv2025

Functional characterization of Ixodes neuropeptide receptors

Neuropeptidergic systems control feeding behaviors in animals, including arthropods. Given the wide variety of pathogens transmitted by ticks during hematophagy, there is an urgency to understand the neural mechanisms responsible for tick feeding behavior. We characterized three Ixodes signaling systems that are involved in feeding regulation in other arthropods: neuropeptide CCHamide (CCHa), short neuropeptide F (sNPF) and sulfakinin. RNAs encoding the preproneuropeptides and their receptors were characterized and cDNAs for the receptors were expressed in HEK293T cells by transient transfection. Activation of the receptors by synthetic peptides was monitored by a calcium release (FLIPR) fluorescence assay. There was a single receptor (CCHaR) activated by CCHa (NH2-SCKMYGHSCLGGH-amide) containing a disulfide bond with an EC50=12 pM, while a scrambled cyclic peptide was inactive at 1 M. Of the two Ixodes NPY-like receptors, NPYLR1A was activated by sNPF (NH2-GGRSPSLRLRF-amide) with an EC50=1.9 nM. NPYLR1B did not respond to 10 M sNPF. A single sulfakinin receptor was activated by a sulfated sulfakinin (NH2-SDDY(SO3H)GHMRF-amide) with an EC50=220 pM but not by 1 M non-sulfated sulfakinin. The Ixodes GPCRs were able to couple to endogenous HEK293T G-protein(s). Surprisingly, human but not Ixodes GNAQ restored CCHaR responsiveness in HEK293T cells with GNAQ/GNA12 disruptions. Quantitative RT-PCR analysis indicated that all three receptors were expressed in the synganglion. CCHaR/CCHa were found at high levels in the midgut from unfed ticks, and CCHaR expression in the midgut was confirmed by RNAScope in situ hybridization. These results establish ligand-receptor identities for three central neuropeptide systems in Ixodes and set the stage for structure-function and physiological investigations.

neuroscience↗

bioRxiv2018

De novo origin of multicellularity in response to predation

The transition from unicellular to multicellular life was one of a few major events in the history of life that created new opportunities for more complex biological systems to evolve. Predation is hypothesized as one selective pressure that may have driven the evolution of multicellularity. Here we show that de novo origins of simple multicellularity can evolve in response to predation. We subjected outcrossed populations of the unicellular green alga Chlamydomonas reinhardtii to selection by the filter-feeding predator Paramecium tetraurelia. Two of five experimental populations evolved multicellular structures not observed in unselected control populations within ~750 asexual generations. Considerable variation exists in the evolved multicellular life cycles, with both cell number and propagule size varying among isolates. Survival assays show that evolved multicellular traits provide effective protection against predation. These results support the hypothesis that selection imposed by predators may have played a role in some origins of multicellularity.

evolutionary biology↗