Merkel cell stimulation in fear and sensory signaling.

Stress and traumatic experiences have significant and lasting effects on sensory systems. We recently identified unique expression of proteins associated with epidermal skin cells (keratinocytes) and mechanosensory Merkel cells (MC) in circulating extracellular vesicles from adult women who had experienced sexual trauma specifically during adolescence, biologically linking trauma exposure with a specific neuron-like skin cell. Here, we aimed to develop and validate a preclinical mouse model utilizing chemogenetic (DREADD Gq) activation of a population of MC. Using a reporter line, we confirmed the expected pattern of the Krt14 Cre in specific MC skin areas and that these tissues expressed relevant MC marker genes similarly between male and female mice. Chemogenetic stimulation of MC produced robust neuronal activation of the insular cortex (IC), a brain region relevant to somatosensory and valence integration. To determine if the mice could detect MC activation, home cage behaviors following CNO treatment significantly increased nest grooming time. Conditioned place preference further revealed an avoidance response following MC stimulation; an effect that was stronger in female mice. Finally, to connect back to our trauma question, we examined MC activation in fear conditioning and identified deficits in fear extinction. Overall, these studies validate utilization of this preclinical model in further investigating the mechanosensory system and its potential involvement in PTSD symptoms and therapeutic interventions. Ongoing studies will focus on critical developmental periods relevant to both MC development and sex differences associated with trauma vulnerability and potential sensory based therapeutic options for PTSD-related symptoms.