title: Corticotropin-releasing factor and Urocortin I modulate excitatory glutamatergic synaptic transmission.
abstract: Corticotropin-releasing factor (CRF)-related peptides serve as hormones and neuromodulators of the stress response and play a role in affective disorders. These peptides are known to alter complex behaviors and neuronal properties, but their receptor-mediated effects at CNS synapses are not well described. Here we show that excitatory glutamatergic transmission is modulated by two endogenous CRF-related peptide ligands, corticotropin-releasing factor [CRF rat/human (r/h)] and Urocortin I (Ucn I), within the central nucleus of the amygdala (CeA) and the lateral septum mediolateral nucleus (LSMLN). These limbic nuclei are reciprocally innervated, are involved in stress and affective disorders, and have high densities of the CRF receptors CRF1 and CRF2. Activation of these receptors exerts diametrically opposed actions on glutamatergic transmission in these nuclei. In the CeA, CRF(r/h) depressed excitatory glutamatergic transmission through a CRF1-mediated postsynaptic action, whereas Ucn I facilitated synaptic responses through presynaptic and postsynaptic CRF2-mediated mechanisms. Conversely, in the LSMLN, CRF caused a CRF1-mediated facilitation of glutamatergic transmission via postsynaptic mechanisms, whereas Ucn I depressed EPSCs by postsynaptic and presynaptic CRF2-mediated actions. Furthermore, antagonists of these receptors also affected glutamatergic neurotransmission, indicating that endogenous ligands tonically modulated synoptic activity at these synapses. These data show that CRF receptors in CeA and LSMLN synapses exert and maintain a significant synaptic tone and thereby regulate excitatory glutamatergic transmission. The results also suggest that CRF receptors may provide novel targets in affective disorders and stress.
authors.affiliation: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555-1031, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Baojian
authors.initials: B
authors.lastname: Yu
authors.forename: Volker
authors.initials: V
authors.lastname: Neugebauer
authors.forename: Dimitri E
authors.initials: DE
authors.lastname: Grigoriadis
authors.forename: Jean
authors.initials: J
authors.lastname: Rivier
authors.forename: Wylie W
authors.initials: WW
authors.lastname: Vale
authors.forename: Patricia
authors.initials: P
authors.lastname: Shinnick-Gallagher
authors.forename: Joel P
authors.initials: JP
authors.lastname: Gallagher
mesh_terms: D000679:Amygdala / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008032:Limbic System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D012686:Septal Nuclei / Q000378:metabolism / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D054832:Urocortins; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D008024:Ligands; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D018698:Glutamic Acid; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone