Abstract
The LC has been implicated in the sleep/wake cycle, attention/alertness, emotional/stress responses, and cognitive processes. In order to make clear the functions of the LC, we developed a novel method to destroy selectively the NA neurons in the LC. Transgenic mice were used that expressed human interleukin 2 receptors (hIL2R) driven by the dopamine-beta hydroxylase (DBH) promoter. One week following stereotaxic microinjection of the immunotoxin (anti-hIL2R antibody conjugated with Psudomonas exotoxin) into the LC of a transgenic mouse, the cell bodies in the LC disappeared totally together with the disruption of NA nerve terminals in the projection fields. No signs of recovery of the ablated LC neurons were noted 4 weeks following immunotoxin injection. The LC-ablated mice spent more time in the open arms in the elevated plus-maze, showed central field preference in the open-field, and buried less number of marbles in the marble burying test, suggestive of the role of the LC in determining the anxiety state of mice. In contrast, plasma ACTH was not significantly different in such stress paradigms as restraint and the immune challenge with LPS injection, suggesting that LC may not play an essential role in transmission of the stress signals to the hypothalamus. Thus, a novel method was developed for selective and thorough destruction of the LC by the immunotoxin-mediated cell targeting, and differential involvements of the LC were disclosed in the anxiety-related behaviors and neuroendocrine stress-responses. [J Physiol Sci. 2008;58 Suppl:S37]
