(140) Investigation of brain regions underlying light-aversive behavior

Abstract

Veterans returning from active duty are at an increased risk for post-traumatic headache (PTH) and migraine. Migraine alone affects 10% of men and 25% of women in the general population and Veterans are at an increased risk for PTH. Sensory abnormalities are present in individuals with PTH and migraine including extreme light and sound sensitivity. Calcitonin gene-related peptide (CGRP) is a critical neuropeptide involved in pain signaling and has recently come to the forefront of migraine pathophysiology where it con-tributes to headache and associated sensory abnormalities. In this study we attempt to identify anatomical regions where CGRP could act to induce light-aversive behavior in migraine and PTH. The posterior thalamus (Po) has been suggested to be a brain region that could integrate light and pain. In addition to the Po, the amygdala has been suggested to play a role in migraine headaches. We hypothesized that CGRP acts as a neuromodulator in the Po and/or the amygdala to induce light aversive behavior. To test this hypothesis, we used targeted approaches to probe areas of the brain thought to be important in the development of photophobia. The first was direct CGRP injection into the Po. The second was optoge-netic stimulation using channelrhodopsin driven by the CaMKII promoter to stimulate either the Po or the amygdala. We found that CGRP injection into and optical stimulation of the Po induced signif-icant light aversive behavior, without increased anxiety in the open field assay. In contrast, optical stimulation of the amygdala did not change light aversion or anxiogenic behavior. These data suggest that stimulation of the Po can induce light aversion associated with CGRP actions, while the amygdala stimulation is not sufficient to induce light-aversive behavior. These results may begin to shed light on the complex circuitry of light-aversive behaviors in mice.