Disorders of the Nervous System
Author: Agostina Stahl | Email: astahl@fmed.uba.ar
Stahl AM1°, Taravini I2° Gomez G3°, López Díaz A1°, Rela L1°, Murer MG1°
1° Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay), UBA-CONICET
2° Instituto de Ciencia y Tecnología de los Alimentos de Entre Ríos (ICTAER-UNER-CONICET), Universidad Nacional de Entre Ríos, Gualeguaychú, Entre Ríos, Argentina.
3° Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States
Parkinson’s disease (PD) motor symptoms arise after striatal dopaminergic denervation and are linked to an imbalance between direct and indirect striatal projection pathways. These pathways are modulated by various striatal interneurons, including cholinergic interneurons that contribute to PD motor symptoms and dyskinesias induced by L-dopa treatment, the standard therapy. Whether striatal interneurons co-expressing somatostatin, NPY, nitric oxide, and GABA (iSOM) contribute to PD symptoms or L-DOPA-induced dyskinesia (LID) remains unknown. Using ex vivo patch-clamp recordings, we examined iSOM spontaneous activity in control, PD and dyskinetic mice. There was a non-significant trend toward increased firing frequency in PD mice and an excitatory effect of the D1/D5 selective agonist SKF81287 in all experimental groups. We also found an increased expression of the activity marker c-Fos in iSOM of PD mice 1 h after finishing a 14-day dyskinetogenic L-dopa treatment. Therefore, we evaluated whether selective inhibition of iSOM using DREADDs could alleviate motor symptoms of PD and LID. After LID was established with a mild dose of L-dopa (6 mg/kg), iSOM inhibition slightly increased LID expression but did not affect locomotor activity or motor deficits. Moreover, inhibiting iSOM alongside L-dopa treatment did not prevent the onset or severity of LID. Given the diverse neurotransmitters released by iSOM, selective ablation may help clarify their role in PD pathology.