Inhibitory Basal Ganglia Inputs Induce Excitatory Motor Signals in the Thalamus Kim, Jeongjin et al. Neuron, Volume 95, Issue 5, 1181 - 1196.e8
Abstract:
Basal ganglia (BG) circuits orchestrate complex motor behaviors predominantly via inhibitory synaptic outputs. Although these inhibitory BG outputs are known to reduce the excitability of postsynaptic target neurons, precisely how this change impairs motor performance remains poorly understood. Here, we show that optogenetic photostimulation of inhibitory BG inputs from the globus pallidus induces a surge of action potentials in the ventrolateral thalamic (VL) neurons and muscle contractions during the post-inhibitory period. Reduction of the neuronal population with this post-inhibitory rebound firing by knockout of T-type Ca2+ channels or photoinhibition abolishes multiple motor responses induced by the inhibitory BG input. In a low dopamine state, the number of VL neurons showing post-inhibitory firing increases, while reducing the number of active VL neurons via photoinhibition of BG input, effectively prevents Parkinson disease (PD)-like motor symptoms. Thus, BG inhibitory input generates excitatory motor signals in the thalamus and, in excess, promotes PD-like motor abnormalities.
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Funding Info:
We thank Dr. K. Deisseroth both for providing the opsin viral vectors and for the learning opportunities offered to J.K. and D.K. by his Optogenetic Workshop; J. Woo and G. Park for experimental assistance and editing; and Dr. W. Heo and Dr. T. Kyung for testing mCherry antibody. This work was supported by grants from the National Leading Research Laboratory Program ( 2016-015167 to D.K.), the World Class Institute (WCI) program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning ( WCI 2009-003 ), as well as by grants from the National Research Foundation of Singapore ( CRP4-2008-01 ) and Ministry of Education (T2-2-095) to G.J.A., the KAIST Future Systems Healthcare Project (to S.-B.P.), and National Research Foundation of Korea (NRF) grants funded by the Korea Government, the Ministry of Science, ICT, and Future Planning ( 2015M3A9A7067220 to K.-H.C.)
Description:
The full paper is freely available at the publisher's URL: https://doi.org/10.1016/j.neuron.2017.08.028