Defining the role of social touch somatosensory neurons in stress response: A novel skin-brain pathway for resilience

Tactile interaction between social mammals is a naturally rewarding stimuli, motivating social bonding and other adaptive behaviors. Socially valanced touch has been shown to have anxiolytic effects and to attenuate stress-related pathophysiology in a phenomenon called “social buffering”. In addition, a lack of social tactile stimulation, particularly during early life, can induce neurobiological changes associated with mood disorders. However, the cellular mechanisms by which social touch mediates stress resilience and affective states are unknown. Therefore, the primary goal of this project is to investigate the role of social touch somatosensory neurons in stress resilience and affective regulation during chronic stress.

Clinically, chronic stress confers higher risk of developing psychiatric disorders such as anxiety, Major Depressive Disorder (MDD), and suicidality. Persistent neuroplastic changes in brain circuits that mediate emotion and reward processing contribute to the etiology of depressive disorders. Therefore, there has been increasing interest in characterizing neurobiological processes that modulate the function of these circuits for potential therapeutic use. Emerging clinical research in humans shows that specialized sensory neurons that respond to gentle rewarding touch (CT-afferents) influence affective aspects of somatosensation. Gentle stroking to activate CT-afferents has been found to alleviate stress-related physiological changes, though mechanistic exploration of this phenomenon in preclinical models has been difficult, as it was unclear if rodents harbor an orthologous neuronal population.

Importantly, the Abdus-Saboor lab has recently identified and characterized a genetically defined cell population in mice called Mrgprb4-lineage sensory neurons, which exhibit similar characteristics to human CT-afferents, including mediating transmission of affective social touch. In recently published work in Cell, the lab has traced these neurons from the skin, through the spinal cord, up to the dopaminergic brainstem nuclei, the Ventral Tegmental Area (VTA) and its downstream projection region, the Nucleus Accumbens (NAc), which is the brain’s major reward processing center. Activation of Mrgprb4-lineage neurons in mice modulates rewarding mating behaviors, influences stress resilience, and induces dopamine release into the NAc [1]. Thus, Mrgprb4-lineage neurons appear to be part of a rewarding skin-brain touch circuit, but it is still unknown if selective activation of Mrgprb4+ neurons has stress-resilient effects similar to CT-afferents, and what role Mrgprb4+ neurons play in central changes during chronic stress. Therefore, I will use a combination of transdermal optogenetic manipulation, in vivo neural imaging, and single cell molecular profiling to examine how Mrgprb4+ neurons modulate the NAc in the context of chronic stress, as well as the efficacy of Mrgprb4+ neuron stimulation in rescuing stress-related behavioral deficits.