Corticostriatal connectivity balance in L-DOPA-induced dyskinesia under and after the acute effect of L-DOPA

ESCANDE, MARIELA VERÓNICA; MURER, MARIO GUSTAVO; KEIFMAN, ETTEL; BELFORTE, JUAN EMILIO; UNGER, JESICA

Buenos Aires

Congreso; SAN 2020 XXXV annual meeting; 2020

Sociedad Argentina de Neurociencia

Striatal medium spiny neurons (MSNs) are key in action selection. A balanced activity of direct pathway MSNs (dMSNs) and indirect pathway MSNs (iMSN) is needed for an appropriate motor performance. Midbrain dopaminergic neurons provide this balance by modulating MSNs? response to cortical inputs. In Parkinson?s disease (PD) nigrostriatal dopaminergic neurons degenerate and an imbalance in favor of iMSNs over dMSNs appears. Chronic treatment with L-DOPA, a DA precursor widely used to treat PD symptoms, causes abnormal movements known as L-DOPA-induced dyskinesia (LID) in up to 30% of patients and is thought to emerge from an imbalance in MSN activity. Under the hypothesis that chronic L-DOPA treatment may produce aberrant plasticity phenomena that affect corticostriatal connectivity that underlie LID, we studied functional and structural changes that emerge from PD and from an acute and chronic L-DOPA treatment. We used in vivo juxtacellular recordings on transgenic mice showing MSN type-specific expression of fluorescent proteins, and we assessed MSN responsiveness to motor cortex stimulation before (off) and following (on) an acute L-DOPA challenge. Off L-DOPA, we did not find differences from PD corticostriatal connectivity. However, on L-DOPA dMSN reverted from their previous disconnection from cortical inputs. Therefore, during LID dMSN prevailed over iMSN. Interestingly, iMSN seemed to contribute less to this imbalance after chronic treatment with L-DOPA.