Neural excitability, synaptic transmission and neuron-glia interactions
Author: Agostina Mónica Stahl | Email: firstname.lastname@example.org
Agostina Stahl 1°, Cecilia Tubert 1°, Analía López Díaz 1°, Lorena Rela 1°, Gustavo Murer 1°
1° Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay) / Universidad de Buenos Aires – CONICET
Parkinson’s disease (PD) is a neurodegenerative disease whose symptoms are caused by loss of nigrostriatal dopaminergic neurons and subsequent changes in striatal circuitry function. Chronic administration of L-dopa remains the gold standard treatment, but patients often develop involuntary movements known as L-dopa-induced dyskinesia (LID). Altered function of striatal interneurons regulating the balance of the striatal projection pathways may be linked to the emergence of PD symptoms and LID. Here, we focus on GABAergic striatal interneurons that also release somatostatin (iSOM). We have seen that LID in PD mice relates to an enhanced expression of the cell activity marker c-Fos in iSOM. Using ex vivo patch-clamp recordings, we are studying iSOM physiology in control, PD and dyskinetic mice. Under control conditions, 64% of iSOM are spontaneously active even after GABAergic and glutamatergic synaptic blockade and exhibit a variety of firing frequencies (from 2 to 20 Hz) and activity patterns (from regular to bursty). Whole-cell recordings show transitions between regular pacemaker-like firing and a burst-pause pattern in individual iSOM. Moreover, some iSOM show very depolarized membrane potentials leading to depolarization block of firing. We are performing cell-attached recordings to assess the effects of dopaminergic denervation and chronic L-dopa treatment on the spontaneous activity of iSOM.