Date of Award

2022

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Neuroscience

First Advisor

Ishmail J. Abdus-Saboor

Abstract

Pleasurable touch during social behavior is key to building familial bonds and meaningful connections. As revealed by a global pandemic, isolation from these social contacts can have devastating effects on mental health. Yet, the identity and role of sensory neurons that transduce social touch remain unknown, limiting our understanding of what makes social touch beneficial and pleasurable, and therefore what goes wrong when it is missing or perturbed. A population of sensory neurons labeled by the G-protein coupled receptor Mrgprb4 detect stroking touch in mice, however, these neurons have never been implicated in any natural social behaviors. Here, we study the social relevance of Mrgprb4-lineage neurons by genetically engineering mice to allow activation or ablation of this population and reveal that these neurons are required for sexual receptivity to male mounts as well as social touch behaviors between females. Even in social isolation, optogenetic stimulation of Mrgprb4-lineage neurons through the back skin is sufficient to induce dopamine release, a conditioned place preference, and a dorsiflexion posture. This dorsiflexion resembles the natural behavioral response to social touch to the back, which is either a lordotic copulatory posture to male mounts, or a crawling posture from cagemate female contact. In the absence of Mrgprb4-lineage neurons, female mice no longer find male mounts rewarding: sexual receptivity is supplanted by aggression and a coincident decline in dopamine release. Together, these findings establish that Mrgprb4-lineage neurons are the first neurons of a skin-to-brain circuit encoding the rewarding quality of social touch. Using the same transdermal optogenetic approach, we also reveal (1) the possibility that these neurons may activate pain pathways in the context of inflammation, potentially implicating them in an allodynia phenotype, and (2) a related population of DRG neurons may provide insight into sex-differences in pain perception, yet further experimentation is necessary.

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