Investigating the role of noradrenaline in behavioral switching using optogenetics

Behera, Leafy (2023) Investigating the role of noradrenaline in behavioral switching using optogenetics. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Leafy Behera (18MS123)) Thesis_18MS123.pdf - Submitted Version Restricted to Repository staff only Download (10MB)

Abstract

Dynamic environmental conditions often require switches in ongoing behaviors in response to new challenges. This ability is a crucial aspect of survival because understanding how animals switch between different behaviors can give us insights about how the brain functions and orchestrates behavior. Most studies investigating behavioral flexibility use task-structured designs, in which behavior is driven by external cues whereas the neural mechanisms underlying uninstructed, spontaneous behaviors remain largely unknown. Studies investigating the role of neuromodulators in behavioral processes indicate that higher levels of noradrenaline increases arousal, promoting switches in behavior. Building upon this hypothesis, we targeted the Locus Coereleus (LC) (a brainstem nuclei and the primary source of noradrenaline in the brain). Since high levels of noradrenaline can induce anxiety, we first established a frequency that could be used to stimulate the LC without inducing anxiety in the mice. We conducted experiments in the open field, where the LC was stimulated at 4Hz while monitoring the movement of the mice. In the open field test the stimulation of noradrenergic cells at 4hz did not induce anxiety but decreased overall locomotion. Since 4Hz did not induce anxiety, we used the frequency to stimulate the LC while the mice were head-fixed and exhibiting different spontaneous behaviors. Closed-loop stimulation of the LC at 4Hz in the VBA setup did not affect the behavior. Interestingly, we observed that only stimulation of the noradrenergic cells did not promote egress, suggesting that the activity of the LC alone does not promote the egress behavior. On the running wheel, we observed that stimulating the LC increased running after the stimulation period. Together, our findings indicate that stimulating the LC at 4Hz does not induce anxiety neither does it promote behavior but 4Hz stimulation does decrease locomotion as observed in the open field and running wheel experiments.

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