Hes5+ astrocytes potentiate primary afferent Aδ and C fiber-mediated excitatory synaptic transmission to spinal lamina I neurons

Astrocytes are critical in regulating synaptic transmission in the central nervous system (CNS). The spinal dorsal horn (SDH) is a crucial region that processes and integrates somatosensory information from the periphery and transmits it to the brain. Our previous work demonstrated that stimulation of an astrocyte population in the SDH, characterized by the expression of hairy and enhancer of split 5 (Hes5), causes pain hypersensitivity. However, the mechanism by which Hes5⁺ astrocytes modulate synaptic transmission in the SDH remains unclear. In this study, using electrophysiological and cell type-specific functional manipulation approaches, we found that chemogenetic stimulation of Hes5⁺ SDH astrocytes enhanced Aδ and C fiber-mediated excitatory postsynaptic currents in lamina I neurons. A pharmacological blockade of the glycine binding site of N-methyl-D-aspartate (NMDA) receptors prevented the astrocytic enhancement. These findings suggest that Hes5⁺ astrocytes in the SDH enhance synaptic transmission from primary afferent nociceptors to lamina I neurons by potentiating NMDA receptor activity.