Low-Threshold Primary Afferent Drive onto GABAergic Interneurons in the Superficial Dorsal Horn of the Mouse

Abstract

Inhibition in the spinal cord dorsal horn is crucial for maintaining separation of touch and pain modalities. Disruption of this inhibition results in allodynia, allowing low-threshold drive onto pain and temperature-sensitive projection neurons. This low-threshold (LT) excitatory pathway is normally under strong inhibition. We hypothesized that superficial dorsal horn inhibitory neurons, which would be ideally located to suppress LT drive onto projection neurons in a feedforward manner, are driven by LT input. In addition, because disinhibition-induced allodynia shares some features with the immature dorsal horn such as elevated sensitivity to LT input, we also questioned whether LT drive onto inhibitory neurons changes during postnatal maturation. To investigate these questions, slices were made at different ages from transgenic mice with enhanced green fluorescent protein expression in GABAergic neurons and whole-cell recordings were made from these fluorescent neurons. Evoked synaptic activity was measured in response to electrical stimulation of the dorsal root. We demonstrate that Abeta fibers activate a significant proportion of superficial dorsal horn GABAergic neurons. This occurs with similar excitatory synaptic drive throughout postnatal maturation, but with a greater prevalence at younger ages. These GABAergic neurons are well situated to contribute to suppressing LT activation of output projection neurons. In addition, the majority of these GABAergic neurons also had convergent input from high-threshold fibers, suggesting that this novel subclass of GABAergic neurons is important for gating innocuous as well as noxious information.