| Description |
Over 26 million people worldwide suffer from Parkinson's Disease, Huntington's Disease, Tourette's Syndrome, and dystonia, neurological disorders which have all been linked to dysfunction of the subcortical brain region known as the basal ganglia. The basal ganglia are a collection of subcortical nuclei that operate on motor, cognitive, and reward signals from the cortex. The basal nuclei act on these cortical signals through three anatomically predominate pathways: a direct pathway that projects to output via one synaptic connection, an indirect pathway that projects through two internal basal nuclei before synapsing onto the output, and a hyperdirect pathway which projects via one, fast excitatory synapse onto basal ganglia output. These three pathways are integrated into a common motor signal at the level of the basal ganglia output: the substantia nigra pars reticulata (SNr) in the rodent. Our incomplete knowledge of the pathway contributions to behavioral outputs and the integration capabilities of the SNr limits our ability to understand and treat basal ganglia dysfunction. In this work, we endeavored to advance the current understanding of signal information integration and transmission through the basal ganglia pathways, specifically by using behavioral biomarkers of pathway activity and investigating integration of the pathways at basal ganglia output. First, we demonstrated that local axon collaterals within the SNr function to control the timing and likely desynchronization of SNr firing at steady state. Next, we discovered that axon collaterals of SNr neurons provide a divisive gain iv control for limited activation durations, and that the scope of this function is limited due to the inadequate conductances provided by the synapses. Finally, we tied individual pathway contributions to SNr responses ex vivo and motor behavior, including an attempt to explain the pathway contributions to the therapeutic mechanisms behind treatment of basal ganglia dysfunction. Overall, our work presented here provides valuable insights into understanding basal ganglia pathway integration and motor behavioral production. |
