Nicotinic Receptor Subtype-Selective Circuit Patterns in the Subthalamic Nucleus

• DOI: 10.1523/jneurosci.3528-14.2015
• Publication Date: 2015-03-04T17:21:50Z
• Authors: Cheng Xiao; Julie M. Miwa; Brandon J. Henderson; Ying Wang; Purnima Deshpande; Sheri L. McKinney; Henry A. Lester
• Keywords: Subthalamic Nucleus; Pars compacta; Pars reticulata

The glutamatergic subthalamic nucleus (STN) exerts control over motor output through nuclei of the basal ganglia. High-frequency electrical stimuli in STN effectively alleviate symptoms movement disorders, and cholinergic stimulation boosts this effect. To gain knowledge about mechanisms modulation STN, we studied cellular circuit aspects nicotinic acetylcholine receptors (nAChRs) mouse STN. We discovered two largely divergent microcircuits STN; these are regulated part by either α4β2 or α7 nAChRs. neurons containing nAChRs (α4β2 neurons) received more inputs, preferentially innervated GABAergic substantia nigra pars reticulata. In contrast, (α7 dopaminergic compacta. Interestingly, local excited a majority (79%) but exerted strong inhibition 58% neurons, indicating an additional diversity neurons: responses to stimulation. Chronic exposure nicotine selectively affects STN: treatment increased number upregulated α4-containing nAChR sensitivity, enhanced firing rate both ex vivo . Thus, chronic enhances function microcircuit involving This indicates agonist as potential pharmacological intervention alter balance between microcircuits, may provide means inhibit neurons.