Corticotropin‐Releasing Hormone Regulates Spontaneous Excitatory Postsynaptic Currents on the Nucleus of the Solitary Tract

Abstract

Corticotropin‐releasing hormone (CRH) plays a critical role in responses to stress. Two major subtypes of CRH receptors (CRHRs), type 1 receptors (CRH1Rs) and CRH type 2 receptors (CRH2Rs), have been identified in the medial nucleus tractus solitarius (mNTS). The goal of this study was to characterize whether CRH alters glutamatergic transmission to NTS neurons receiving arterial chemoreceptor afferent inputs. Whole‐cell recordings of NTS second‐order neurons identified by DiA labeling of carotid bodies were obtained in caudal NTS slices (250μM thick). Slices were incubated with 100nM CRH in aCSF for 20 minutes and spontaneous miniature excitatory postsynaptic currents (mEPSCs) were recorded under voltage clamp 1–3 hours later. Control slices were treated with aCSF alone. Pre‐treatment with CRH (100nM) significantly increased mEPSCs amplitude (p<0.01) from 20.7 ± 1.0 pA to 25.1 ± 1.1 pA, with no change in frequency (control: 2.2 ± 0.2 Hz; CRH: 3.1 ± 0.4 Hz, p>0.05). Pretreatment with the CRH antagonist astressin (100nM–1μM) for 10 minutes and then in combination with CRH for another 20 minutes attenuated the CRH‐induced increase in mEPSC amplitude to 19.3 ±1.3 pA (p<0.01). mEPSCs observed following application of CRH were abolished by the non‐NMDA glutamate receptor antagonist CNQX (20μM). These studies indicate that CRH has a direct effect on NTS neurons through postsynaptic CRHRs.Support or Funding InformationThis work supported by PO1 HL88052