Article
Effect of harmaline on neuronal activity in cerebellar Purkinje cells in a genetic mouse model of tremor
Effekte von Harmalin auf die neuronale Aktivität von Purkinje-Zellen des Kleinhirns in einem genetischen Mausmodell für Tremor
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Published: | June 26, 2020 |
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Objective: Harmaline-induced tremor by activation of GABAA receptors is a commonly used model of essential tremor. Clinical and experimental findings suggest that altered cerebellar function is involved in tremor generation. The atypical chemokine receptor 1 (Ackr1) is exclusively expressed in cerebellar Purkinje cells (PCs). It has been shown that Ackr1−/− knock out (KO) mice are sensitive to develop harmaline induced tremor.
To investigate potential differences in cerebellar neuronal activity of PCs in wild type (Wt) and Ackr1−/− KO mice, and the effect of harmaline.
Methods: We recorded single unit (SU) activity together with local field potentials (LFPs) under urethane anesthesia (1.6 g/kg, i.p.) in Ackr1−/− KO mice (N=8) and Wt control mice (N=9) before and after harmaline injection (15mg/kg).
Results: A total of 1736 cerebellar PCs were recorded from Wt and KO mice. The PCs neuronal firing rate was higher and the dispersion of index as a measure for irregularity was lower in Wt mice compared to KO mice (P<0.001). Harmaline decreased the firing rate and increased the dispersion index without differences in KO and Wt mice (P<0.001). The percentage of regular firing patterns was lower and the burst pattern was higher in KO compared to Wt mice (P<0.001). Injection of harmaline increased the burst patterns in both Wt and KO mice (P<0.05). The relative power of cerebellar theta, alpha, and beta band activity was lower, while gamma was higher in KO as compared to Wt mice. Harmaline-injection enhanced theta band activity in both Wt and KO mice (P<0.001), whereas beta band activity was enhanced, and gamma band activity was reduced only in KO mice (P<0.001).
Conclusion: Neuronal activity of PC cells differed between Wt and KO mice both with regard to single unit firing patterns and relative power of oscillatory activity. Overall, harmaline-injection affected neuronal activity, which was not specific for KO mice.