Changes in Excitability Properties of Ventromedial Motor Thalamic Neurons in 6-OHDA Lesioned Mice

The activity of basal ganglia input receiving motor thalamus (BGMT) makes a critical impact on motor cortical processing, but modification in BGMT processing with Parkinsonian conditions has not be investigated at the cellular level. Such changes may well be expected because of homeostatic regulation of neural excitability in the presence of altered synaptic drive with dopamine depletion. We addressed this question by comparing BGMT properties in brain slice recordings between control and unilaterally 6-hydroxydopamine hydrochloride (6-OHDA)-treated adult mice. At a minimum of one month after 6-OHDA treatment, BGMT neurons showed a highly significant increase in intrinsic excitability, which was primarily because of a decrease in M-type potassium current. BGMT neurons after 6-OHDA treatment also showed an increase in T-type calcium rebound spikes following hyperpolarizing current steps. Biophysical computer modeling of a thalamic neuron demonstrated that an increase in rebound spiking can also be accounted for by a decrease in the M-type potassium current. Modeling also showed that an increase in sag with hyperpolarizing steps found after 6-OHDA treatment could in part but not fully be accounted for by the decrease in M-type current. These findings support the hypothesis that homeostatic changes in BGMT neural properties following 6-OHDA treatment likely influence the signal processing taking place in the BG thalamocortical network in Parkinson's disease.