The Rostral Ventrolateral Medulla Input to Central Amygdala Regulates Anxiety-Like Behaviors in Mice for Chronic Light Exposure.

backgroundEmerging evidence increasingly links environmental light exposure to the development of anxiety disorder. The rostral ventrolateral medulla (RVLM), a key brainstem center that regulates sympathetic outflow and blood pressure (BP), has been implicated in the autonomic dysregulation frequently observed in anxiety. High blood pressure is a recognized exacerbating factor for anxiety-related pathology. Although aberrant projections from the central amygdala (CeA) to brainstem regions have been reported in multiple mood disorders, it remains unclear whether the CeA receives input from the RVLM and to what extent the RVLM's excitation influences anxiety symptoms induced by chronic light exposure (CL).

methodsWe employed a chronic mild light (250-300 lx) for 4 weeks to induce anxiety-like behaviors in mice. Using a tail-cuff system and ELISA assay, we assessed CL mice's BP and plasma catecholamine levels. Immunofluorescence was utilized to unravel the neuronal c-fos expression in the RVLM and CeA. Combining retrograde virus tracing technology, chemogenetic and optogenetic manipulations in freely moving mice to examine the effects of regulating RVLM-CeA pathway on anxiety-like behaviors induced by chronic light.

resultsChronic light exposure in mice induces elevated blood pressure and elevated neuronal activity, which are more pronounced in the RVLM than in the CeA. Chemogenetic inhibition of RVLM neurons markedly attenuated CL-induced anxiety-like behaviors. Moreover, optogenetic inhibition of the RVLM→CeA pathway reduced anxiety phenotypes in CL-exposed mice, whereas optogenetic activation of this pathway in normal mice acutely triggered anxiety-like behaviors.

conclusionsThese findings demonstrate that the enhanced excitatory signaling within the RVLM→CeA circuit underlies the development of anxiety-like behaviors induced by chronic light, revealing a novel mechanism by which the RVLM regulates light-related affective dysfunction.