Effects of chronic social isolation on somatosensory circuit development and behaviors

Abstract

Light touch is critical for social communication across the lifespan for humans and other mammals. The COVID-19 pandemic demonstrates how social and sensory inputs, including touch, are deprived due to chronic social isolation, which can be detrimental to our mental and physical health. Previous studies on animal models of chronic social isolation have demonstrated various behavioral changes, while the relationship between changes in tactile circuits and other complex behaviors remain unclear. Light touch processing from the body skin is initiated through the activation of low-threshold mechanoreceptor neurons (LTMRs), which synapse onto heterogeneous populations of spinal cord interneurons and projection neurons that process and transmit tactile information to the brain. In addition, corticospinal neurons with cell bodies in the primary somatosensory cortex innervate the spinal cord dorsal horn; through connections with a range of spinal cord interneurons, corticospinal neurons play a significant role in the gating of touch information and act as a ‘filter’ to selectively control which tactile information ascends to higher brain centers. Whether and how chronic social isolation affects the development of tactile circuits and behaviors is of particular interest of my thesis study. Using conditional mouse genetics, histology, electrophysiology, and behavioral assays, we found that chronic social isolation during the post-weaning period leads to profound behavioral changes, as well as anatomical, and functional changes in somatosensory circuits. We found that post-weaning social isolation leads to behavioral hyperreactivity to innocuous light touch stimuli. We also found that post-weaning social isolation leads to an increased number and increased firing rates of spinal cord neurons in response to light touch stimuli. Further, we found that post-weaning social isolation leads to decreased corticospinal neuron innervations in the spinal cord dorsal horn, as well as decreased firing rates of spinal cord neurons in response to direct somatosensory cortex stimulation. More specifically, we found that post-weaning social isolation leads to decreased firing rates of spinal cord inhibitory parvalbumin (PV) interneurons in response to somatosensory cortex stimulations, suggesting that post-weaning social isolation weakens the connections between corticospinal neurons and inhibitory PV interneurons that ultimately causes tactile hypersensitivity in mice. In line with this, modulating distinct subsets of spinal cord interneurons, such as inhibitory Ror𝛽 interneurons and excitatory PV interneurons, might be sufficient to affect tactile sensitivities. Together, this work reveals the importance of social touch during post-weaning development in governing the normal development of tactile behaviors and circuits in mice.