Abstract

The dorsal horn (DH) of the spinal cord contains a heterogenous population of neurons that process incoming sensory signals before information ascends to the brain. We have recently characterized calretinin-expressing (CR+) neurons in the DH and shown that they can be divided into excitatory and inhibitory subpopulations. The excitatory population receives high-frequency excitatory synaptic input and expresses delayed firing action potential discharge, whereas the inhibitory population receives weak excitatory drive and exhibits tonic or initial bursting discharge. Here, we characterize inhibitory synaptic input and neuromodulation in the two CR+ populations, in order to determine how each is regulated. We show that excitatory CR+ neurons receive mixed inhibition from GABAergic and glycinergic sources, whereas inhibitory CR+ neurons receive inhibition, which is dominated by glycine. Noradrenaline and serotonin produced robust outward currents in excitatory CR+ neurons, predicting an inhibitory action on these neurons, but neither neuromodulator produced a response in CR+ inhibitory neurons. In contrast, enkephalin (along with selective mu and delta opioid receptor agonists) produced outward currents in inhibitory CR+ neurons, consistent with an inhibitory action but did not affect the excitatory CR+ population. Our findings show that the pharmacology of inhibitory inputs and neuromodulator actions on CR+ cells, along with their excitatory inputs can define these two subpopulations further, and this could be exploited to modulate discrete aspects of sensory processing selectively in the DH.

Highlights

  • The dorsal horn (DH) of the spinal cord is a key region for processing sensory signals from skin, joints, muscle and viscera (Todd, 2010)

  • A significant barrier to understanding how this processing takes place has been the substantial heterogeneity among the interneurons that populate the DH and the lack of information about how specific interneuron subpopulations participate in sensory processing (Graham et al, 2007)

  • Comparisons of inhibitory synaptic input were carried out on Typical and Atypical CR+ neurons identified according to their dendritic morphology in acute parasagittal slices, validated in a subset of successfully recovered neurons

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Summary

Introduction

The dorsal horn (DH) of the spinal cord is a key region for processing sensory signals from skin, joints, muscle and viscera (Todd, 2010). Other groups have used genetic ablation, or chemo-genetic activation/ inactivation to show that certain interneuron subpopulations in the DH play precise roles in sensory processing under both normal and pathological conditions (Duan et al, 2014; Foster et al, 2015; Peirs et al, 2015; Petitjean et al, 2015). This effort is assembling information on how specific populations of DH interneurons interact in spinal circuits to shape sensory experience (Smith et al, 2014)

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