α1-adrenergic receptor regulation of excitatory transmission in the bed nucleus of the stria terminalis: characterization, mechanism, and potential role in disease

Abstract

Synaptic plasticity is proposed to be a molecular mechanism underlying multiple forms of learning. The modulation of synaptic plasticity, therefore, may have profound consequences over behavior and may mediate pathological conditions. This project examined synaptic modulation via the activation of α1-adrenergic receptors (α1-ARs) in the bed nucleus of the stria terminalis (BNST), a brain region involved in reward, addiction and anxiety behaviors. I found that in the BNST, α1-ARs induce a heterosynaptic long term depression (LTD) of excitatory transmission that is maintained postsynaptically and requires the activation of L-type voltage gated calcium channels and the functional desensitization of calcium permeable AMPA receptors. Furthermore, this plasticity is disrupted in both behavioral and genetic models of affective disorders suggesting it may play a role in the pathology of these disorders. These data add to the recent evidence suggesting that the α1-AR may be an excellent target for therapeutic intervention in several affective disorders.