Control of excitability in striatal cholinergic interneurons: mechanism underlying IsAHP

CECILIA TUBERT; GONZALO SANCHEZ; MARIO GUSTAVO MURER; LORENA RELA

Huerta Grande, Córdoba

Congreso; XXVII Congreso Anual SAN; 2012

Sociedad Argentina de Investigación en Neurociencias

Parkinson's disease is a neurodegenerative disorder caused by nigrostriataldopaminergic neuron loss. Acetylcholine released by a small population oftonically active interneurons (ChIs), is a main modulator of striatal function.Tonic activity in ChIs depends on intrinsic mechanisms. Action potentials openK+ channels, either KCa or Kv, leading to an afterhyperpolarization (AHP) withthree phases: fAHP, mAHP, and sAHP. Molecular mechanisms that mediateIsAHP in ChIs are still unknown, but it is supposed to be Ca2+ dependent.Previous work shows that a reduction of IsAHP results in hyperactive ChIs in arat model of Parkinson's disease, which is seen as a lack of 'accommodation'.Thus, IsAHP may be a novel target to treat the hypercholinergic state inParkinson's disease. Here we study the maturation and pharmacology of IsAHPin ChIs from mouse brain slices. Accommodation and IsAHP in ChIs wereinsensitive to UCL2077, a blocker of atypical KCNQ K+ channels, but they werestrongly reduced by margatoxin, a blocker of voltage-gated K+ channels withselectivity for Kv1.3 channels. Thus, our data suggest a novel voltagedependentcomponent of IsAHP in ChIs which needs further validation as atherapeutic target in animal models of Parkinson's disease.