The striatum is widely viewed as the fulcrum of pathophysiology in Parkinson’s disease (PD) and L- DOPA-induced dyskinesia (LID). In these two closely related dopamine-dependent disease states, the balance in activity of striatal direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) is thought to be disrupted, leading to aberrant action selection. This view is based upon the dichotomous dopaminergic modulation of these two pathways through D1 and D2 receptors. However, current models of these states do not account for the propensity of neural circuits to homeostatically correct sustained perturbations in activity. To determine if homeostatic mechanisms were engaged in PD and LID models, SPNs were studied in /ex vivo /brain slices. These studies revealed that SPNs manifested homeostatic adaptations in intrinsic excitability and excitatory corticostriatal connectivity to re-balance average activity in both PD and LID models. However, synaptic strength was not homeostatically scaled in parallel, potentially leading to inappropriately timed and scaled activity. This aberrant activity should be particularly prominent in LID models where both iSPNs and dSPNs undergo substantial synaptic reorganization. Strategies for ameliorating these pathological
adaptations will be discussed.