5-HT2C Receptor Knockdown in the Amygdala Inhibits XXXX and Behaviors.

@entity308 @entity148 @entity750 @entity158 @entity35 @entity9
Neuroplasticity in the amygdala drives @entity158 . The central nucleus (CeA) serves major amygdala output functions and can generate emotional-affective behaviors and modulate nocifensive responses. The CeA receives excitatory and inhibitory inputs from the basolateral nucleus (BLA) and @entity750 receptor subtype 5-HT2CR in the BLA, but not CeA, has been implicated anxiogenic behaviors and @entity148 . Here, we tested the hypothesis that 5-HT2CR in the BLA plays a critical role in CeA plasticity and @entity9 behaviors in the @entity35 spinal nerve ligation (SNL) model. Local 5-HT2CR knockdown in the BLA with stereotaxic injection of 5-HT2CR shRNA AAV vector decreased vocalizations and @entity148 - and @entity308 -like behaviors and increased sensory thresholds of SNL @entity35 , but had no effect in sham controls. Extracellular single-unit recordings of CeA neurons in anesthetized @entity35 showed that 5-HT2CR knockdown blocked the increase in neuronal activity (increased responsiveness, irregular spike firing, and increased burst activity) in SNL @entity35 . At the synaptic level, 5-HT2CR knockdown blocked the increase in excitatory transmission from BLA to CeA recorded in brain slices from SNL @entity35 using whole-cell patch-clamp conditions. Inhibitory transmission was decreased by 5-HT2CR knockdown in control and SNL conditions to a similar degree. The findings can be explained by immunohistochemical data showing increased expression of 5-HT2CR in non-GABAergic BLA cells in SNL @entity35 . The results suggest that increased 5-HT2CR in the BLA contributes to @entity9 -related amygdala plasticity by driving synaptic excitation of CeA neurons. As a rescue strategy, 5-HT2CR knockdown in the BLA inhibits neuropathic- @entity158 .SIGNIFICANCE STATEMENT Neuroplasticity in the amygdala has emerged as an important @entity158 mechanism. This study identifies a novel target and rescue strategy to control abnormally enhanced amygdala activity in an animal model of @entity9 . Specifically, an integrative approach of gene transfer, systems and brain slice electrophysiology, behavior, and immunohistochemistry was used to advance the novel concept that @entity750 receptor subtype 5-HT2C contributes critically to the imbalance between excitatory and inhibitory drive of amygdala output neurons. Local viral vector-mediated 5-HT2CR knockdown in the amygdala normalizes the imbalance, decreases neuronal activity, and inhibits neuropathic- @entity158 . The study provides valuable insight into @entity750 receptor (dys)function in a limbic brain area.
