title: mGluR8 modulates excitatory transmission in the bed nucleus of the stria terminalis in a stress-dependent manner.
abstract: Metabotropic glutamate receptors (mGluRs) are important modulators of excitatory transmission, and have been implicated in anxiety and stress-related behaviors. Previously, we showed that group III mGluR agonists could depress excitatory synaptic transmission in the bed nucleus of the stria terminalis (BNST), an integral component of the anxiety circuitry. Here, we provide converging evidence indicating that this effect is mediated primarily by mGluR8, is exerted presynaptically, and is modulated by noradrenergic signaling and stress. The effects of the group III mGluR agonist L-AP4 on excitatory transmission are not potentiated by the mGluR4-selective allosteric potentiator PHCCC, but are mimicked by the mGluR8-selective agonist DCPG. Consistent with these results, mGluR8-like immunoreactivity is seen in the BNST, and the actions of L-AP4 on excitatory transmission are absent in slices from mGluR8 knockout (KO) mice. Application of DCPG is associated with an increase in paired-pulse evoked glutamate synaptic currents, and a decrease in spontaneous glutamate synaptic current frequency, consistent with a primarily presynaptic action. mGluR8-mediated suppression of excitatory transmission is disrupted ex vivo by activation of α1 adrenergic receptors (α1 ARs). BNST mGluR8 function is also disrupted by both acute and chronic in vivo exposure to restraint stress, and in brain slices from α2A AR KO mice. These studies show that mGluR8 is an important regulator of excitatory transmission in the BNST, and suggest that this receptor is selectively disrupted by noradrenergic signaling and by both acute and chronic stress.
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors: Heather B
authors: HB
authors: Gosnell
authors: Yuval
authors: Y
authors: Silberman
authors: Brad A
authors: BA
authors: Grueter
authors: Robert M
authors: RM
authors: Duvoisin
authors: Jacob
authors: J
authors: Raber
authors: Danny G
authors: DG
authors: Winder
mesh_terms: D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*; D012686:Septal Nuclei / Q000187:drug effects / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C111435:metabotropic glutamate receptor 8