Esther Vinner1, Michal Israelashvili1, Izhar Bar-Gad2. 1. Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, Israel. 2. Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, Israel. Electronic address: izhar.bar-gad@biu.ac.il.
Abstract
BACKGROUND: Experimental findings and theoretical models have associated Tourette syndrome with abnormal striatal inhibition. The expression of tics, the hallmark symptom of this disorder, has been transiently induced in non-human primates and rodents by the injection of GABAA antagonists into the striatum, leading to temporary disinhibition. NEW METHOD: The novel chronic model of tic expression utilizes mini-osmotic pumps implanted subcutaneously in the rat's back for prolonged infusion of bicuculline into the dorsolateral striatum. RESULTS: Tics were expressed on the contralateral side to the infusion over a period of multiple days. Tic expression was stable, and maintained similar properties throughout the infusion period. Electrophysiological recordings revealed the existence of tic-related local field potential spikes and individual neuron activity changes that remained stable throughout the infusion period. COMPARISON WITH EXISTING METHODS: The striatal disinhibition model provides a unique combination of face validity (tic expression) and construct validity (abnormal striatal inhibition) but is limited to sub-hour periods. The new chronic model extends the period of tic expression to multiple days and thus enables the study of tic dynamics and the effects of behavior and pharmacological agents on tic expression. CONCLUSIONS: The chronic model provides similar behavioral and neuronal correlates of tics as the acute striatal disinhibition model but over prolonged periods of time, thus providing a unique, basal ganglia initiated model of tic expression. Chronic expression of symptoms is the key to studying the time varying properties of Tourette syndrome and the effects of multiple internal and external factors on this disorder.
BACKGROUND: Experimental findings and theoretical models have associated Tourette syndrome with abnormal striatal inhibition. The expression of tics, the hallmark symptom of this disorder, has been transiently induced in non-human primates and rodents by the injection of GABAA antagonists into the striatum, leading to temporary disinhibition. NEW METHOD: The novel chronic model of tic expression utilizes mini-osmotic pumps implanted subcutaneously in the rat's back for prolonged infusion of bicuculline into the dorsolateral striatum. RESULTS: Tics were expressed on the contralateral side to the infusion over a period of multiple days. Tic expression was stable, and maintained similar properties throughout the infusion period. Electrophysiological recordings revealed the existence of tic-related local field potential spikes and individual neuron activity changes that remained stable throughout the infusion period. COMPARISON WITH EXISTING METHODS: The striatal disinhibition model provides a unique combination of face validity (tic expression) and construct validity (abnormal striatal inhibition) but is limited to sub-hour periods. The new chronic model extends the period of tic expression to multiple days and thus enables the study of tic dynamics and the effects of behavior and pharmacological agents on tic expression. CONCLUSIONS: The chronic model provides similar behavioral and neuronal correlates of tics as the acute striatal disinhibition model but over prolonged periods of time, thus providing a unique, basal ganglia initiated model of tic expression. Chronic expression of symptoms is the key to studying the time varying properties of Tourette syndrome and the effects of multiple internal and external factors on this disorder.
Authors: Julia A K Chartove; Michelle M McCarthy; Benjamin R Pittman-Polletta; Nancy J Kopell Journal: PLoS Comput Biol Date: 2020-02-25 Impact factor: 4.475