GABAB receptor plasticity in corticotrophin releasing hormone neurons in the paraventricular nucleus during chronic unpredictable stress

Abstract

GABAB (γ‐aminobutytic acid type B) receptor is important in the regulation of neuronal excitability. Chronic stress leads to hyperactivity of corticotrophin releasing hormone (CRH) neurons. However, the role of GABAB receptors in the regulation of CRH neurons in paraventricular nucleus (PVN) of the hypothalamus in chronic stress is not known. Here, we determined pre‐ and postsynaptic GABAB receptor function in identified PVN‐CRH neurons expressing eGFP driven by crh premotor‐driven eGFP. Whole cell patch‐clamp recording were performed on PVN‐CRH neurons in brain slices from unstressed rats and rats with chronic unpredictable mild stress (CUMS). Bath application of the GABAB receptor agonist baclofen induced a significant lesser reduction of firing activity in PVN‐CRH neurons in CUMS than in unstressed rats. Furthermore, baclofen induced lesser outward currents in PVN‐CRH neurons in CUMS than in unstressed rats. Baclofen‐induced currents were eliminated by inclusion of GDP‐β‐s in internal recording solution or blocking G protein‐coupled inwardly‐rectifying K (GIRK) channels with tertiapin. GABAB1 receptor expression level in the PVN was significantly decreased in CUMS than in unstressed rats. Baclofen produced significant greater inhibition of the frequency of glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitor postsynaptic currents (IPSCs) without affecting the amplitude of EPSCs and IPSCs in PVN‐CRH neurons in CUMS and unstressed rats. These data suggest that down‐regulated postsynaptic GABAB receptor contributes to suppressing GABAB‐mediated inhibition of PVN‐CRH neurons in chronic stress.Support or Funding InformationNIMH grants MH096086.