Parkinson's disease (PD) is a complex neurodegenerative movement disorder. The central pathological feature of PD is the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, that project to the dorsal striatum. The resulting dopamine deficiency in this area dysregulates the striatal neural net, causing the motor deficits of PD patients. However, the process leading dopamine's depletion into neural deficits and how it can reflect on cortical activity is still largely unknown. This project's goal is to investigate the electrophysiological and functional changes affecting the primary motor cortex following dopaminergic depletion in a PD mouse model induced by 6-OHDA unilateral injection in striatum. Furthermore, through in vivo wide-field imaging technique, we aim to evaluate parvalbuminergic (PV) cortical functional connectivity and cortical dopamine fluctuations. Last, any cortical plasticity phenomena induced by the lesion are investigated thorough immunohistochemical analysis. Our preliminary results show an altered asymmetrical PV-mediated cortical activity and an imbalance between excitation and inhibition with an increased excitatory-inhibitory ratio and a sex-related difference in plasticity markers in motor cortex. Ongoing experiments with a robotic platform (M-Platform) for motor rehabilitation during electrophysiological sessions allow to study the potential post-lesion neuroplastic rearrangement. In conclusions, we intensively investigated the alteration in cortical activity following dopaminergic depletion with electrophysiological, functional connectivity and molecular analysis identifying the motor cortex as a potential therapeutic target for PD.