Abstract:
Alcoholism and alcohol abuse is a severe problem. An increase in the blood ethanol concentration affects the function of many parts of the brain, including the Basal Ganglia, which is critical for goal directed and habitual behavior. The Globus Pallidus (GP) is a part of the Basal Ganglia and funnels the output from the striatum, the input part of the Basal Ganglia. The GP is further divided into the internal Globus Pallidus (GPi) and external Globus Pallidus (GPe). There is compelling evidence suggesting that the pathological activity of GPe contributes to the motor symptoms of a variety of movement disorders like Parkinson’s disease, and that GPe activity is affected by ethanol. Recently it was discovered that the GPe is comprised of multiple cell types, with an activity based subdivision into prototypical neurons and arkypallidal neurons. This distinction is important because the firing rate of arkypallidal neurons is lower than that of prototypical neurons. Furthermore, arkypallidal neurons innervates the striatum, resulting in negative feedback, whereas the prototypical neuron innervates the sub thalamic nucleus which is an output pathway. Ethanol affects the open probability of the calcium dependent potassium channel (BKCa) and reduces the firing rate of the arkypallidal, but not prototypical neurons. We computationally modeled these neurons in the neural modeling software MOOSE to determine the factors causing the difference in the firing rate. My results show that the three channels demonstrated to differ between the two neuron types (Hernandez et.al 2015) are not enough to explain the difference in the firing rate of the two neurons but there are other channels which are responsible for the lower firing rate of the arkypallidal neuron. To simulate the effect of ethanol, we increased the BKCa current and the results showed that the firing rate decreased when the BKCa current increased only in the arkypallidal neurons that have a substantially higher BKCa density. In summary, based on our simulations, we argue that there are other factors that affect the firing rate of the GP neuron and provides a foundation for further studies to determine the difference between the prototypical and arkypallidal GP neuron and the effect ethanol has on the neurons.
