Project Summary/Abstract The somatosensory dorsal horn comprises an array of neuronal populations that receive sensory information from the skin. In recent years, the development of transcriptomic and intersectional genetic tools has allowed the characterization of these populations in young adult animals with respect to their distinct molecular identities and functional roles in the processing and transmission of touch, pain and itch information. Preliminary data indicate that the survival of neurons in the dorsal horn of adult mice is dependent on excitatory input from touch receptors in the skin. This has implications for the processing of somatosensory information during aging, in which the transmission of touch information is impaired by demyelination and by the loss of mechanosensory end organs including Merkel cells (Feng et al., 2018). Chronic silencing Merkel cells in young adult Atoh1CreERT2; Piezo2f/f mice results in the apoptotic loss of excitatory and inhibitory dorsal horn neurons by 20-25%, with some molecularly defined populations being highly susceptible to cell death and others being resistant. A similar pattern of neuronal cell loss by apoptosis is detected in the dorsal horn of 2-year-old mice. The objective of this proposal is to characterize activity-dependent changes to the cellular composition of the spinal dorsal horn during aging and to determine the functional consequences of dorsal horn remodeling for the execution of sensorimotor behaviors as animals age. These experiments will (1) selectively perturb activity in different classes of cutaneous afferent to identify inputs that support cell survival in adult mice; (2) identify dorsal horn populations, defined by molecular profile, that are maintained by input from the periphery; (3) identify molecularly defined dorsal horn populations that are reduced in size during aging; (4) test the hypothesis that the reduction in the size of the neuronal population marked by expression of Cck and Sst