Synaptic gating of viscerosensory signals in the solitary tract nucleus

Abstract

Inhibitory input at the solitary tract nucleus (NTS) is thought to alter autonomic reflex performance. Somatostatin (SOM) neurons are a class of inhibitory interneuron within the central nervous system and present within the NTS. Here we aimed to quantify the impact inhibition had on vicerosensory signal throughput within the NTS. Using a SOM‐Channel rhodopsin 2‐YFP mouse model, we took whole cell recordings from NTS neurons in horizontal brain stem slices that contained both the NTS and solitary tract (ST). This model allowed the specific activation of the SOM inhibitory network within NTS via ChR2. First we targeted SOM‐ChR2‐YFP positive neurons to characterise LED pulse parameters and assay boundaries. Each LED pulse (465 nm, 10 mW) evoked one action potential regardless of pulse duration (0.5 to 100 ms). We then recorded neurons randomly to determine if they received ST input and/or SOM input. LED pulses evoked consistent action potential dependent IPSCs in recorded neurons. Where all (n=42) exhibited LED‐evoked IPSCs and none exhibited LED‐evoked EPSCs or exhibited ChR2 currents. LED‐evoked IPSC amplitude increased with LED duration indicating converging inhibitory input at these NTS neurons. Combined, these data indicate SOM input to NTS neurons is exclusively inhibitory and that though SOM neurons are relatively sparse, SOM efferents synapse extensively throughout the NTS. Shocks to the solitary tract evoked low jitter EPSCs that identified second order NTS neurons. We demonstrated that almost all randomly sampled neurons were second order. Some SOM‐ChR2‐YFP neurons also received direct ST input and additional inhibitory input from other SOM interneurons. We investigated the neurotransmitters and post synaptic receptors involved and find LED‐evoked IPSCs were both GABA and glycine mediated. This finding was surprising as glycinergic transmission has not been described in the medial NTS previously. In current clamp studies, we determined the impact of SOM input on action potential (AP) generation and throughput. LED‐IPSPs prevented spontaneous AP firing when neurons were depolarized and delayed AP onsets in response to current injections. LED‐IPSPs also prevented ST‐evoked AP firing, effectively dropping throughput from 86.7 to 6.7%. Combined, these data indicate that an extensive inhibitory network exists within the NTS that likely operates to coordinate or alter autonomic reflex function.