title: Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism.
abstract: Striatal cholinergic interneurons show tonic spiking activity in the intact and sliced brain, which stems from intrinsic mechanisms. Because of it, they are also known as "tonically active neurons" (TANs). Another hallmark of TAN electrophysiology is a pause response to appetitive and aversive events and to environmental cues that have predicted these events during learning. Notably, the pause response is lost after the degeneration of dopaminergic neurons in animal models of Parkinson's disease. Moreover, Parkinson's disease patients are in a hypercholinergic state and find some clinical benefit in anticholinergic drugs. Current theories propose that excitatory thalamic inputs conveying information about salient sensory stimuli trigger an intrinsic hyperpolarizing response in the striatal cholinergic interneurons. Moreover, it has been postulated that the loss of the pause response in Parkinson's disease is related to a diminution of I(sAHP), a slow outward current that mediates an afterhyperpolarization following a train of action potentials. Here we report that I(sAHP) induces a marked spike-frequency adaptation in adult rat striatal cholinergic interneurons, inducing an abrupt end of firing during sustained excitation. Chronic loss of dopaminergic neurons markedly reduces I(sAHP) and spike-frequency adaptation in cholinergic interneurons, allowing them to fire continuously and at higher rates during sustained excitation. These findings provide a plausible explanation for the hypercholinergic state in Parkinson's disease. Moreover, a reduction of I(sAHP) may alter synchronization of cholinergic interneurons with afferent inputs, thus contributing to the loss of the pause response in Parkinson's disease.
authors.affiliation: Systems Neuroscience Section, Department of Physiology and Biophysics, School of Medicine, University of Buenos Aires, Buenos Aires C1121ABG, Argentina. neurofis@fmed.uba.ar
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Sanchez
authors.forename: Mariano Julian
authors.initials: MJ
authors.lastname: Rodriguez
authors.forename: Pablo
authors.initials: P
authors.lastname: Pomata
authors.forename: Lorena
authors.initials: L
authors.lastname: Rela
authors.forename: Mario Gustavo
authors.initials: MG
authors.lastname: Murer
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D001205:Ascorbic Acid / Q000009:adverse effects; D001464:Barium / Q000494:pharmacology; D003198:Computer Simulation; D003342:Corpus Striatum / Q000293:injuries / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007395:Interneurons / Q000502:physiology*; D008297:Male; D008959:Models, Neurological; D018696:Neuroprotective Agents / Q000494:pharmacology; D016627:Oxidopamine / Q000009:adverse effects; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000293:injuries / Q000502:physiology
chemical_list: C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D007211:Indoles; D018696:Neuroprotective Agents; D011725:Pyridines; D001030:Apamin; D001464:Barium; D016627:Oxidopamine; C061017:linopirdine; D000109:Acetylcholine; D001205:Ascorbic Acid