ePoster

Lesions of the lateral hypothalamus-nigral projection result in motor deficits in rats: Implications for Parkinson’s disease

Asena Bingul, Sam Merlin, Simon Killcross, Teri Furlong
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Asena Bingul, Sam Merlin, Simon Killcross, Teri Furlong

Abstract

The lateral hypothalamus (LH) is emerging as a brain region of interest in Parkinson’s disease (PD). Specifically, the LH neuron populations have been shown to degenerate in PD, thus undergoing neuron loss like the substantia nigra (SN) which is a defining feature of PD that is thought to underlie observed motor symptoms. Interestingly, the LH has strong anatomical projections to the SN, but the behavioural functions associated with this projection have not been determined. We have recently shown that the LH is involved in habitual instrumental responding and spontaneous locomotor activity in rats; behaviours that are also known to be altered in SN-models of PD. Thus, we sought to determine whether the LH communicates with the SN to promote these behaviours. To do so, we utilised rats to functionally disconnect the LH and SN by infusing a shRNA virus and 6-hydroxydopamine toxin, respectively. Rats were then tested for the ability to develop habits in an instrumental learning task, and motor abilities on tasks typically used to model PD motor deficits. The results showed that disconnection of LH and SN does not disrupt habitual-motor learning or motor coordination on the balance beam. However, it significantly impacted locomotor activity in the open-field test, forelimb paw use in the cylinder test, and motor coordination in the rotarod test. Our findings suggest that the LH and SN work together to regulate motor behaviour in rats, and thus degeneration of the LH seen in PD may also contribute to motor symptoms of the disease.

Unique ID: fens-24/lesions-lateral-hypothalamus-nigral-604bc468