Differential effects of corticotropin-releasing hormone (CRH) on the properties of GABAergic and non-GABAergic neurons of the nucleus tractus solitarii (nTS)

Peripheral cardiorespiratory reflexes in response to a variety of stressors are processed and integrated in the nucleus tractus solitarii (nTS). In addition, the paraventricular nucleus of the hypothalamus (PVN) significantly contributes to the regulation of cardiorespiratory function, in part, through its nTS projections that contain CRH. Within the nTS, we have shown that CRH increases overall nTS activity and influences the cardiorespiratory response to hypoxia. However, the impact of CRH on the specific phenotype of neurons within the nTS remains unclear. We hypothesized the overall excitatory influence of CRH on nTS function is due to its excitation of non-GABAergic (glutamatergic) and/or inhibition of GABAergic nTS neurons. Male and female transgenic GAD1-EGFP mice [strain FVB-Tg (GadGFP) 45704Swn/J, Jackson Laboratory, 4-5 weeks] was used to identify GABAergic and non-GABAergic neurons. The influence of CRH on synaptic neurotransmission to monosynaptic GABAergic and non-GABAergic nTS neurons, and the expression of CRH receptors was determined. Synaptic events were examined during exogenous CRH (300nM) and/or CRH receptor block (CRHR-x, Astressin 100nM). In the presence of CRH, network-driven spontaneous (s) EPSC amplitude decreased in GABAergic neurons yet not in non-GABAergic neurons. sEPSC frequency was not altered in either group. CRH also attenuated the amplitude of afferent (TS)-evoked EPSCs in GABAergic neurons yet enhanced the amplitude in non-GABAergic neurons. CRHR-x prior to application of CRH ablated the synaptic responses in both phenotypes. GABA neurons were tonically influenced by CRH, as CRHR-x increased TS-ESPC amplitude. CRH-positive fibers were adjacent to GABA and non-GABAergic nTS neurons (immunohistochemistry). While the total expression of CRHR2 mRNA was more prevalent than CRHR1 within the entire nTS, CRHR1 expression primarily occurred in GABA neurons within the intermediate nTS compared to CRHR2 (RNAScope). Altogether, our data shows that the influence of CRH on nTS activity is dependent on neuron phenotype, and GABA neurons are under tonic inhibitory CRH influence. The activation of CRH projections from PVN to nTS likely promotes the excitation of nTS via an increase in excitation and a decrease in inhibition. HL166183 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.