Distinct forms of Gq-receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress.

McElligott ZA, Klug JR, Nobis WP, Patel S, Grueter BA, Kash TL, Winder DG
Proc Natl Acad Sci U S A. 2010 107 (5): 2271-6

PMID: 20133871 · PMCID: PMC2836642 · DOI:10.1073/pnas.0905568107

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.

MeSH Terms (19)

Alcoholism Animals Ethanol Glutamic Acid GTP-Binding Protein alpha Subunits, Gq-G11 Humans Long-Term Synaptic Depression Male Mice Mice, Inbred C57BL Neuronal Plasticity Norepinephrine Receptor, Angiotensin, Type 1 Receptor, Metabotropic Glutamate 5 Receptors, AMPA Receptors, Metabotropic Glutamate Septal Nuclei Signal Transduction Stress, Physiological

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