The Role of Orexin in Social Behaviour

Date
2022-09
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Abstract
Social behaviour is essential to the survival of most organisms and is produced by complex neural systems. The hypothalamus is known to be crucial for survival and reproduction. Recent research into the neural substrates of social behaviours has identified that hypothalamic regions play a fundamental role in the regulation of social behaviour by driving internal states of arousal, attention, and motivation. Hypocretin (Hcrt)/orexin-expressing neurons in the lateral hypothalamus (LH) are critical for the regulation of arousal and motivated behaviours. Hcrt neurons are widely studied with respect to their function in the regulation of these internal states however, there is limited knowledge for their role in social behaviour. We hypothesized that the LH Hcrt neurons have a fundamental role in social interaction and tested this hypothesis with a combination of fiber photometry and optogenetic experiments in a novel Hcrt-Cre-C57BL6/J mouse line. We found that the activity of the LH Hcrt neuron population increases following approach to social conspecifics. The increase in activity was significantly greater during approach to a novel conspecific rather than a familiar one, and in males compared to females. Using a familiar/novel object interaction test, we then determined that this differential increase was specific to social stimuli. Optogenetic inhibition of Hcrt neuron activity caused male mice to spend significantly less time socially interacting suggesting a disruption in normative social behaviour. This effect of optogenetic inhibition was absent in females. Finally, we validated that the effect of Hcrt neuron inhibition on social behaviour was not due to changes in anxiety-like or locomotor behaviours. In sum, these findings provide strong evidence for the role of hypocretin neurons in social behaviour, particularly in male mice.
Description
Keywords
hypocretin, orexin, social, behaviour, rodent, mouse, photometry, optogenetics
Citation
Dawson, M. (2022). The role of orexin in social behaviour (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.