Lateral hypothalamic galanin neurons are activated by stress and blunt anxiety-like behavior in mice.

Despite the prevalence of anxiety disorders, the molecular identity of neural circuits underlying anxiety remains unclear. The lateral hypothalamus (LH) is one brain region implicated in the regulation of anxiety, and our recent data found that chemogenetic activation of LH galanin neurons attenuated the stress response to a novel environment as measured by the marble burying test. Thus, we hypothesize that LH galanin neurons may contribute to anxiety-related behavior. We used chemogenetics and fiber photometry to test the ability of LH galanin neurons to influence anxiety and stress-related behavior. Chemogenetic activation of LH galanin neurons significantly decreased anxiety-like behavior in the elevated plus maze, open field test, and light dark test. However, LH galanin activation did not alter restraint stress induced HPA activation or freezing behavior in the fear conditioning paradigm. In vivo calcium monitoring by fiber photometry indicated that LH galanin neurons were activated by anxiogenic and/or stressful stimuli including tail suspension, novel mouse interaction, and predator odor. Further, in a fear conditioning task, calcium transients strongly increased during foot shock, but were not affected by the unconditioned stimulus tone. These data indicate that LH galanin neurons both respond to and modulate anxiety, with no influence on stress induced HPA activation or fear behaviors. Further investigation of LH galanin circuitry and functional mediators of behavioral output may offer a more refined pharmacological target as an alternative to first-line broad pharmacotherapies such as benzodiazepines.

Parsing the neural correlates of anxious apprehension and anxious arousal in the grey-matter of healthy youth.

Neuroscientific and psychological research posits that there are two transdiagnostic facets of anxiety: anxious arousal and anxious apprehension. Though these two facets of anxiety are distinct, they are often subsumed into one domain (e.g., trait anxiety). The primary goal of the current study was to delineate the relationship between anxious arousal and cortical thickness versus the relationship between anxious apprehension and cortical thickness in a sample of typically functioning youth. The secondary aim was to determine where in the brain cortical thickness significantly correlated with both components of anxiety. Results indicated that the right anterior insula has a stronger relationship to anxious arousal, whereas the dorsolateral prefrontal cortex and left anterior insula were found to correlate with both anxious arousal and apprehension. We also observed volumetric differences in the amygdala and hippocampus between anxious arousal and anxious apprehension. Whereas anxious arousal, but not apprehension, predicted left amygdala volume, anxious apprehension, but not arousal, predicted right hippocampal volume. These findings demonstrated that there are both differences and similarities in the neural regions that contribute to independent facets of anxiety. Results are discussed in terms of previous findings from the affective and developmental cognitive neurosciences.