Excitability of striatal cholinergic interneurons

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

Ventura CA

Congreso; First Gordon Research Conference on Basal Ganglli: Basal Ganglia Cells and Circuits in Health and Disease; 2014

First Gordon Research Conference on Basal Ganglli: Basal Ganglia Cells and Circuits in Health and Disease

Striatal cholinergic interneurons (ChINs) code salient stimuli through a brief silencing of tonic firing -known as the pause response- likely involving the activation of an intrinsic potassium conductance. Experimental parkinsonism associates with a loss of the pause response and the emergence of hyperexcitability in ChINs. Our earlier reports showed that hyperexcitability becomes evident as a reduction in spike frequency adaptation and a delay in the eventual silencing (spike accommodation) of adult rat ChINs in response to sustained depolarizing current pulses, after a lesion to dopaminergic neurons. Interestingly, the hyperexcitable phenotype of ChiNs in lesioned rats resembled the observed in juvenile ChiNs. Here we show that the developmental change in excitability was reproduced in mouse ChINs. A deeper analysis shows that juvenile ChINs show a bimodal distribution in terms of accommodation that is absent in the adult, in which a marked accommodation is the prevalent feature. In addition, we present evidence that estimations of spike frequency adaptation and spike accommodation do not correlate well and may involve divergent mechanisms. Pharmacological manipulations to block KCNQ/Kv7 potassium channels, which have been implicated in slow afterhyperpolarization currents of hippocampal neurons, showed no evidence of participation of these targets in either spike frequency adaptation or accommodation of ChINs. Together, our results suggest that more than one mechanism controlling excitability of ChINs may become impaired after loss of dopaminergic neurons.