Identification of touch neurons underlying dopaminergic pleasurable touch and sexual receptivity

Abstract

Pleasurable touch during social behavior is the key to building familial bonds and meaningful connections. One form of social touch occurs during sex. Although sexual behavior is initiated in part by touch, and touch is ongoing throughout copulation, the identity and role of sensory neurons that transduce sexual touch remain completely unknown. A population of sensory neurons labeled by the G-protein coupled receptor Mrgprb4 detect stroking touch in mice. Here, we study the social relevance of this population by genetically engineering mice to allow activation or ablation of Mrgprb4-lineage neurons and reveal that these neurons are required for sexual receptivity and sufficient to activate reward circuitry. Even in social isolation, optogenetic stimulation of Mrgprb4-lineage neurons through the back skin is sufficient to induce a conditioned place preference and a striking lordosis-like copulatory posture in females. 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 dopaminergic release in the mesolimbic reward pathway. In addition to sexual behavior, Mrgprb4-lineage neurons are also required for social postures induced by female-to-female back touch. Together, these findings reveal a skin-to-brain circuit encoding the rewarding quality of social touch.

A critical role for touch neurons in a skin-brain pathway for stress resilience

“…DREADD-mediated activation of these peripheral neurons altered activity in brain areas linked to reward and emotional processing. These two sets of experiments, congruent with previous work from the lab 22 , suggest that Mrgprb4-lineage neurons act on affect-relevant brain circuits.…”

“…At 9-10Hz, the VTA is leading by 41ms +/-5.5ms in control mice but by only 16ms+/-2.6ms in Mrgprb4 Cre ; Rosa DTA mice (Fig5 C-F). Given this interesting difference, and our prior findings connecting Mrgprb4-lineage neurons to brain reward areas 22 , we decided to direct our attention to the VTA-Nac circuit. The dopaminergic inputs from VTA to NAc drive reward signaling 46,47 and are altered in Mrgprb4 Cre ; Rosa DTA mice (Fig5F).…”

“…In the present study, we sought to determine (1) the long-term effects of early-life ablation of Mrgprb4 lineage touch neurons on behavior and neurophysiology and (2) the rescue potential of Mrgprb4-lineage neuron activation on stress-induced behaviors and hormonal changes in adulthood. Based on the importance of Mrgprb4-lineage neurons in social reward 22 and the emotional consequences of touch or the lack thereof across species, we hypothesized that the developmental ablation of Mrgprb4-lineage neurons would increase the stress response in adulthood, and that their activation would be therapeutic during stress. Our findings indicate that Mrgprb4-lineage neurons play a critical role in stress resilience and that their activation can reduce the endocrine response to mild stress.…”

A hypothalamic node for the cyclical control of female sexual rejection

“…From a neural perspective, it is long established that the ventrolateral region of the ventromedial hypothalamus (VMHvl) holds a crucial role in the control of female sexual receptivity: besides receiving male-derived information, such as olfactory signals 2,[12][13][14] or the flank somatosensory stimulation derived from copulation attempts 15,16 , electrical stimulation of the VMHvl increases lordosis display while its electrolytic lesion has the opposite effect 7,8 . In addition, the expression of receptors for female sex hormones estrogen (E) and progesterone (P) is observed in a vast percentage of VMHvl neurons (ER+ and PR+ neurons) 11,12 .…”

Chronic pain mediated changes in the appetitive value of affective gentle touch in mice

“…These homeostatic drives, with respect to tactile sensations, are critical for survival as they ensure the promotion of behaviours that allow us to escape harmful stimuli and gravitate towards evolutionarily beneficial stimuli. [1][2][3][4] This includes aversive motivation to escape pain and appetitive motivation towards pleasant touch. [4][5][6] Despite this polarity in motivational valence the distinction between aversive pain and appetitive touch can become blurred in various pathological conditions.…”