Research Highlight:

Stress, Placticity, and Abuse

Original Research Article:
ZA McElligott, JR Klug, WP Nobis, S Patel, BA Grueter, TL Kash and DG Winder (2010). Distinct forms of Gq-receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress. PNAS. 107 (5): 2271-2276.

The bed nucleus of the stria terminalis (BNST), a key nucleus within the “extended amygdala”, is anatomically poised in both the reward and stress circuitry. Given this unique position, the BNST has become a focal point of studies interested in exploring the link between anxiety and addiction. In this nucleus, long-term depression (LTD) plays a critical role in monitoring excitatory influence over circuits which impact cognition and emotional behavior. Previous evidence suggested that both noradrenergic and glutamatergic initiated Gq-coupled signaling in the BNST converge on a final common mechanism for LTD maintenance. McElligott et al. provide evidence to the contrary. While norepinephrine induced LTD via α1-adrenergic receptors (α1-AR) occurs in the same neurons as glutamate-induced LTD (mGluR5-LTD), α1-AR mediated LTD transpires exclusively through the downregulation of calcium permeable AMPA receptors. mGluR5-dependent LTD, however, does not involve the regulation of calcium permeable AMPA receptors. Importantly, these differences are emphasized by the fact that the persistence of these two distinct forms of LTD can be impacted differentially by environmental challenges. For example, α1-AR dependent LTD is disrupted by stress and is resistant to disruption by cocaine. While, on the other hand, mGluR5 dependent LTD is susceptible to cocaine-induced disruptions but is resilient to stress challenges. The authors extend these findings by further demonstrating that the α1-AR dependent LTD can also be diminished by chronic ethanol exposure. Together, these data suggest that in the BNST noradrenergic- and glutamate- activated Gq-coupled initiated signaling is delicately tuned to specific stimuli. Thus, these distinct pathways allow for fine differential control of glutamate synapse efficacy in response to stress.