Key points• Perception of normal bodily sensations relies on the precise regulation of sensory information entering the dorsal horn of the spinal cord.• Inhibitory, axoaxonic, synapses provide a mechanism for this regulation, but the source of these important inhibitory connections remains to be elucidated.• This study shows that a subpopulation of spinal interneurons that expresses parvalbumin and have specific morphological, connectivity and functional characteristics are a likely source of the inhibitory inputs that selectivity regulate non-noxious tactile input in the spinal cord.• Our findings suggest that a loss of normal function in parvalbumin positive dorsal horn neurons may result in the development of tactile allodynia, where non-painful stimuli gain the capacity to evoke the sensation of pain.Abstract Axo-axonic synapses on the central terminals of primary afferent fibres modulate sensory input and are the anatomical correlate of presynaptic inhibition. Although several classes of primary afferents are under such inhibitory control, the origin of these presynaptic inputs in the dorsal horn is unknown. Here, we characterize the neurochemical, anatomical and electrophysiological properties of parvalbumin (PV)-expressing cells in wild-type and transgenic mice where enhanced green fluorescent protein (eGFP) is expressed under the PV promoter. We show that most PV cells have either islet or central cell-like morphology, receive inputs from myelinated primary afferent fibres and are concentrated in laminae II inner and III. We also show that inhibitory PV terminals in lamina II inner selectively target the central terminals of myelinated afferents (∼80% of 935 PVeGFP boutons) and form axo-axonic synapses (∼75% of 71 synapses from PV boutons). Targeted whole-cell patch-clamp recordings from PVeGFP positive cells in laminae II and III showed action potential discharge was restricted to the tonic firing and initial bursting patterns (67% and 33% respectively; n = 18), and virtually all express I h subthreshold voltage-gated currents (94%; n = 18). These neurons show higher rheobase current than non-eGFP cells but respond with high frequency action potential discharge upon activation. presynaptic input on to myelinated primary afferents. Consequently PV cells are ideally placed to play an important role in the development of central sensitization and tactile allodynia.

Highlights► HCN4 channel expression in selected fast-spiking spinal interneuron populations. ► HCN4 channels expressed in most fast-spiking hippocampal interneurons. ► HCN4 channels rarely expressed in regular- or gap-firing interneurons. ► HCN channelopathies now implicated in neurodegenerative diseases and chronic pain.