Optogenetic Activation of Striatal Neurons

Lecture Centre Concourse

Medium spiny neurons (MSNs) make up more than 95% of the cells in the striatum and because of this they are the main structures for specific information processing operations in the striatum. MSNs can be separated into two subpopulations based on their dopamine receptor expression and projections. Some express D1 dopamine receptors and send information to the substantia nigra and are called D1-MSNs. D1-MSNs trigger movement execution when they are activated. Others express D2 receptors and send information to the globus pallidus and are called D2-MSNs. D2-MSNs trigger movement termination when activated. Previously, our lab has shown that mice that lack the neuronal glutamate transporter EAAC1, a mutation that is also seen in patients with obsessive compulsive disorder (OCD), repeatedly performed stereotyped activities controlled by D1-MSNs. This hyperactivity of D1-MSNs could be caused by decreased GABAergic inhibition onto these cells. We have also seen in electrophysiology recordings that D1-MSNs receive weaker GABAergic inputs in the absence of EAAC1. We know that D1-MSNs and D2-MSNs receive GABAergic inputs from other MSNs and other local GABAergic interneurons, but we do not know which types of GABAergic inputs are responsible for the D1-MSNs receiving weaker inputs. Here we optimize an experimental strategy to stimulate these inputs separately using light activation of channelrhodopsin 2 (ChR2), a light-gated ion channel that can be used in neuroscience for light-induced activation of specific cells. Currently, our data show that we can successfully transfect our cells and stimulate D1- and D2-MSNs using ChR2 activation. We have also seen that as we increase the light intensity on ChR2, the responses exhibited by the MSNs increase as well. Ultimately, our findings will provide more insight on striatal hyperactivity in OCD.