I want to improve our understanding of Parkinson's Disease (PD), a devastating illness that affects more than 6 million people. The anatomical hallmark of PD is the degeneration of the dopaminergic neurons of the substantia nigra, which have rich projections to the basal ganglia. The output nuclei of the basal ganglia have shown an abnormal degree of synchronized oscillation in PD which is absent in controls, and so there is a lot of interest in understanding what is happening in this circuit. The external globus pallidus (GPe) is a structure that is at the center of the basal ganglia circuit, and, as such, it is important to understand how it functions. Spike-timing dependent plasticity (STDP) is an interesting phenomenon that modulates the activity of circuits by changing the connection strengths between neurons, and has been characterized in many brain structures. Thus far, it has not been shown to occur in the GPe, and no characterization of STDP in the GPe is yet possible for that reason. Therefore, it is my goal to show and then characterize STDP in the GPe. In order to do this, I will do STDP experiments in rat brain slices.
For the last year or so, I have concentrated on the development of a general method to reduce the complexity and computational load of morphologically and biophysically realistic neuron models. So far, I have reduced a GPe neuron model from 585 to 6 compartments and also a model of a neuron of the deep cerebellar nuclei (DCN) from 517 to 6 compartments, yielding nearly 100-fold increases in computational speed. The reduced models maintain essentially the same FI curve, spike shape, and response to distributed synaptic input. This method will help us to develop realistic, but computationally feasible network simulations of various brain structures. These network simulations will help us to understand the mechanisms behind the functional activity seen in physiological experiments.
My plans for the immediate future are to submit a methods article by the end of the summer detailing the process of reducing biologically realistic neuron models; this paper will also include some analysis of the specific reduced models that I have built (PRC's, axial currents, etc). After I have finished writing this article, I plan to write an NRSA pre-doctoral fellowship application, in which I will propose to study the mechanisms of STDP in the GPe in rat brain slice.