Nicotinic receptor subtype-selective circuit patterns in the subthalamic nucleus

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Cheng XiaoHenry A Lester

Abstract

The glutamatergic subthalamic nucleus (STN) exerts control over motor output through nuclei of the basal ganglia. High-frequency electrical stimuli in the STN effectively alleviate motor symptoms in movement disorders, and cholinergic stimulation boosts this effect. To gain knowledge about the mechanisms of cholinergic modulation in the STN, we studied cellular and circuit aspects of nicotinic acetylcholine receptors (nAChRs) in mouse STN. We discovered two largely divergent microcircuits in the STN; these are regulated in part by either α4β2 or α7 nAChRs. STN neurons containing α4β2 nAChRs (α4β2 neurons) received more glutamatergic inputs, and preferentially innervated GABAergic neurons in the substantia nigra pars reticulata. In contrast, STN neurons containing α7 nAChRs (α7 neurons) received more GABAergic inputs, and preferentially innervated dopaminergic neurons in the substantia nigra pars compacta. Interestingly, local electrical stimuli excited a majority (79%) of α4β2 neurons but exerted strong inhibition in 58% of α7 neurons, indicating an additional diversity of STN neurons: responses to electrical stimulation. Chronic exposure to nicotine selectively affects α4β2 nAChRs in STN: this treatment increased the number of...Continue Reading

Citations

Feb 24, 2015·Neuropharmacology·Melissa L SinkusSherry Leonard
Feb 4, 2016·The European Journal of Neuroscience·Daniel J HegemanC Savio Chan
Mar 21, 2018·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Tora Bonnevie, Kareem A Zaghloul
Apr 22, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yiwen LuanChunyi Zhou
Feb 6, 2018·Experimental and Therapeutic Medicine·Jiao ChenYuan Zhang

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