Central terminals of primary afferents coordinate the spontaneous activity of dorsal horn neurons.

Central terminals of primary afferents and dorsal horn neurons usually exhibit spontaneous activity, the two phenomena being interrelated. Spontaneous activity may constitute a system for adjusting the level of excitation of spinal circuits and the processing of somatosensory information. Superficial dorsal horn neurons fire action potentials in a coordinated form, giving rise to population events. These population events are altered by peripheral inflammation, suggesting their implication in central sensitisation. In this work, we aimed to define the role of primary afferents in the occurrence of this coordinated activity. Channelrhodopsin-2, archaerhodopsin-3 or the hM4Di-DREADD receptor were expressed in primary afferents by Cre-recombination under control of the advillin promoter. Dorsal roots and superficial dorsal horn neurons were simultaneously recorded using in vitro spinal cord slices from neonatal mice. Depolarisation of primary afferents by activation of channelrhodopsin-2 inhibited dorsal root activity and the coordinated firing of dorsal horn neurons. DREADD activation reduced the activity in the afferents and depressed coordinated activity in dorsal horn neurons. In contrast, hyperpolarisation of afferents by archaerhodopsin-3 augmented dorsal root responses and increased the coordinated activity of spinal neurons. The present results demonstrate a direct implication of primary afferents in the generation of coordinated spontaneous firing in superficial dorsal horn neurons. KEY POINTS: The input of somatosensory information through primary afferents is a process subjected to regulation at the level of the spinal cord, even before it reaches second-order neurons. Primary afferent and spinal cord neurons exhibit spontaneous activity, which is altered in pathological models of pain. This study demonstrates the role of primary afferents as a fundamental coordinating element for the spontaneous activity of dorsal horn neurons. These results show that modulating the activity of the central terminals of primary afferents may have profound implications in both the excitability of spinal cord circuits and the processing of somatosensory information.