Neuropeptide Y and corticotropin-releasing factor bi-directionally modulate inhibitory synaptic transmission in the bed nucleus of the stria terminalis.
Neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) have opposing effects on stress and anxiety. Both can modify synaptic activity through their binding to NPY receptors (YRs) and CRF receptors (CRFRs) respectively. The bed nucleus of the stria terminalis (BNST) is a brain region with enriched expression of both NPY and YRs and CRF and CRFRs. A component of the "extended amygdala", the BNST is anatomically well-situated to integrate stress and reward-related processing in the CNS, regulating activation of the hypothalamic-pituitary-adrenal (HPA) axis and reward circuits. Using whole-cell recordings in a BNST slice preparation, we found that NPY and CRF inhibit and enhance GABAergic transmission, respectively. Pharmacological experiments suggest that NPY depresses GABAergic transmission through activation of the Y2 receptor (Y2R), while both pharmacological and genetic experiments suggest that CRF and urocortin enhance GABAergic transmission through activation of the CRF receptor 1 (CRFR1). Further, the data suggest that NPY acts to regulate GABA release, while CRF enhances postsynaptic responses to GABA. These results suggest potential anatomical and cellular substrates for the robust behavioral interactions between NPY and CRF.
Kash
Thomas L
TL
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA.
Winder
Danny G
DG
D000704:Analysis of Variance; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009478:Neuropeptide Y / Q000494:pharmacology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010446:Peptide Fragments / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000172:deficiency; D012686:Septal Nuclei / Q000166:cytology*; D009435:Synaptic Transmission / Q000187:drug effects*; D054832:Urocortins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C471210:2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine; D000814:Aniline Compounds; C101531:CRF receptor type 2; D018756:GABA Antagonists; D009478:Neuropeptide Y; D010446:Peptide Fragments; D011724:Pyridazines; D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C062924:neuropeptide Y (13-36); D005680:gamma-Aminobutyric Acid; D003346:Corticotropin-Releasing Hormone; C049853:gabazine