Distinct forms of Gq-receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress.
Long-term depression (LTD) is an important synaptic mechanism for limiting excitatory influence over circuits subserving cognitive and emotional behavior. A major means of LTD induction is through the recruitment of signaling via G(q)-linked receptors activated by norepinephrine (NE), acetylcholine, and glutamate. Receptors from these transmitter families have been proposed to converge on a common postsynaptic LTD maintenance mechanism, such that hetero- and homosynaptic induction produce similar alterations in glutamate synapse efficacy. We report that in the dorsolateral and ventrolateral bed nucleus of the stria terminalis (BNST), recruitment of G(q)-linked receptors by glutamate or NE initiates mechanistically distinct forms of postsynaptically maintained LTD and these LTDs are differentially regulated by stress exposure. In particular, we show that although both mGluR5- and alpha(1)-adrenergic receptor (AR)-dependent LTDs involve postsynaptic endocytosis, the alpha(1)-AR-initiated LTD exclusively involves modulation of signaling through calcium-permeable AMPA receptors. Further, alpha(1)-AR- but not mGluR5- dependent LTD is disrupted by restraint stress. alpha(1)-AR LTD is also impaired in mice chronically exposed to ethanol. These data thus suggest that in the BNST, NE- and glutamate-activated G(q)-linked signaling pathways differentially tune glutamate synapse efficacy in response to stress.
Department of Psychiatry, Kennedy Center for Human Development, Vanderbilt Brain Institute, Vanderbilt University Medical Center,Nashville, TN 37232, USA.
Zoé A
ZA
McElligott
Jason R
JR
Klug
William P
WP
Nobis
Sachin
S
Patel
Brad A
BA
Grueter
Thomas L
TL
Kash
Danny G
DG
Winder
D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D000431:Ethanol / Q000633:toxicity; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D012686:Septal Nuclei / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D013312:Stress, Physiological
C578935:GRM5 protein, human; C578936:Grm5 protein, mouse; D044140:Receptor, Angiotensin, Type 1; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D000431:Ethanol; D018698:Glutamic Acid; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D009638:Norepinephrine