GABAergic regulation of the centromedian thalamus and control of cortical gamma band oscillations in the mouse

GABAergic regulation of the centromedian thalamus and control of cortical gamma band oscillations in the mouse
R. E. BrownJ. T. McKennaC. YangL. ChenM. GambleA. HulversonP. WoodJ. G. MCCOY김보원최지현
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Vegetative and minimally conscious states (VS/MCS) are devastating conditions which involve severe deficits in brain arousal, occurring as a result of vascular, traumatic or metabolic insults. Improved function in VS/MCS patients following application of drugs affecting the basal ganglia or electrical stimulation of the centromedian thalamus (CM) suggests the possibility for rational treatments. In particular, paradoxical excitation caused by the hypnotic, Zolpidem, in VS/MCS patients may be due to increased inhibition of GABAergic basal ganglia inputs to CM (Schiff, 2010). Thus, development of novel, rational treatments for VS/MCS requires a better understanding of GABAergic inputs to CM and the effects of CM on cortical activity. Accordingly, here we investigate this circuit in mice. Application of the retrograde tracer, Fluorogold (0.5-1 %), into CM in wild-type mice (n=4) confirmed that CM receives major inputs from regions containing GABAergic neurons, including a basal ganglia output nucleus, the substantia nigra pars reticulata (SNr), as well as from the thalamic reticular nucleus (TRN). Immunohistochemical staining for the calcium binding protein, parvalbumin (PV), revealed that ~40 % of the inputs from TRN and SNr were PV-positive. Whole-cell patch-clamp recordings from CM neurons showed that the GABAB receptor agonist, baclofen, reduced the frequency of spontaneous inhibitory synaptic currents to 57 % of control (n=4, p=0.05). Optogenetic stimulation of CM in isoflurane anesthetized mice expressing channelrhodopsin2 constitutively in the thalamus (Thy1-ChR2-EYFP mice) revealed increases in cortical power which were particularly pronounced in frontal regions and at gamma band frequencies (40, 50 Hz). Thus, as in humans, the CM receives GABAergic inputs from the basal ganglia as well as from TRN and increased activity of CM enhances frontal cortical activity typical of conscious states.
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