Previous single-nucleus RNA sequencing (snRNA-seq) analyses from our group in a 6-hydroxydopamine (6-OHDA) mouse model of Parkinson’s disease (PD) identified major striatal cell types and their transcriptional responses to dopaminergic denervation and L-DOPA-induced dyskinesia (LID). In the present work, we aimed to explore with higher detail the transcriptional signatures of direct and indirect spiny projection neurons (SPN), the two major pathways of the basal ganglia circuitry. Given that dSPN from the dorsolateral part of the striatum have been implicated in LID, we refined the previous analysis by subclustering neuronal populations according to their compartmentalization and spatial distribution. By removing residual low-quality nuclei, we obtained a high-resolution characterization of their transcriptional profiles across conditions, focusing on differentially expressed genes (DEGs) and cellular pathways involved in dopaminergic loss and LID. Data suggest that denervation may reduce dSPN excitability, while increasing iSPN excitability, disrupting direct/indirect pathway balance. L-DOPA seemed to reorganize dSPN transcription, including genes involved in synaptic plasticity, lipid metabolism, and calcium homeostasis, while iSPNs showed reduced synaptic activity and changes in potassium transport. In the poster, we will further discuss the compartment- and subtype-specific transcriptional changes that may help uncover neuronal mechanisms in PD and LID.