Control of somatosensory behavior by a subpopulation of spinal dorsal horn astrocytes

Abstract

Astrocytes are critical regulators of CNS function. It has recently been proposed that astrocytes are a heterogeneous population in the developing CNS. However, whether there are regionally and functionally distinct populations of astrocytes in adulthood and if so, whether they play a role in behavior are unknown. Here we identify a population of astrocytes located in superficial lamina in the adult spinal dorsal horn (supSDH). In vivo imaging revealed that supSDH astrocytes increased intracellular Ca²⁺ levels following noxious stimulation such as by capsaicin. To examine the role of astrocytic Ca²⁺ increases in somatosensory behavior, we chemogenetically increased Ca²⁺ in supSDH astrocytes produce pain hypersensitivity to light mechanical stimulation. However, such astrogliogenic hypersensitivity was not induced by stimulating astrocytes located in SDH deeper lamina. Moreover, mechanical hypersensitivity following intraplantar capsaicin was prevented by lacking IP₃R2, an IP₃R subtype that critically contributes to astrocytic Ca²⁺ responses. Our findings identify a regionally restricted astrocyte population in the supSDH that powerfully modulates neuronal processing of mechanical information.