Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Neuroscience

Supervisor

Dr. Mandar Jog

2nd Supervisor

Dr. Nagalingam Rajakumar

Joint Supervisor

Abstract

In advanced stages of Parkinson Disease (PD), gait and postural abnormalities emerge. These symptoms are not prominent at early stages of PD despite significant dopaminergic neuronal loss. Gait abnormalities are largely not responsive to levodopa. Therefore, other types of neurons might be responsible for gait abnormalities of the PD.

Since the reticulospinal tract (RET) is mainly implicated in the control of axial muscles, the degeneration of this pathway or populations of neurons controlling this pathway might be responsible for axial symptoms. However, there is limited data about the neurons controlling the RET. Our aim in this study is to delineate these pathways.

We found that serotonergic projections from dorsal raphe nucleus (DRN) exert an important control on the RET. Inhibition of the DRN resulted in severe episodes of gait freezing in rats. Activation of 5HT1A receptors in the gigantocellular neurons changes muscle tone in rats during gait. The DRN also sends projections to the mesencephalic locomotor region, which are implicated in controlling dynamic gait parameters. DRN neurons receive nigral dopaminergic projections and post-mortem studies in PD patients have identified significant loss of DRN neurons; therefore DRN neurons may play a role in the pathophysiology of gait abnormalities of PD.

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