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 Gq-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 Gq-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 α1- adrenergic receptor (AR)-dependent LTDs involve postsynaptic endocytosis, the α1-AR-initiated LTD exclusively involves modulation of signaling through calcium-permeable AMPA receptors. Further, α1-AR- but not mGluR5- dependent LTD is disrupted by restraint stress. α1-AR LTD is also impaired in mice chronically exposed to ethanol. These data thus suggest that in the BNST, NE- and glutamate-activated Gq-linked signaling pathways differentially tune glutamate synapse efficacy in response to stress.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Feb 2 2010|
- Calcium-permeable AMPA receptor
- Metabotropic glutamate receptor
ASJC Scopus subject areas