title: Nicotinic and opioid receptor regulation of striatal dopamine D2-receptor mediated transmission.
abstract: In addition to dopamine neuron firing, cholinergic interneurons (ChIs) regulate dopamine release in the striatum via presynaptic nicotinic receptors (nAChRs) on dopamine axon terminals. Synchronous activity of ChIs is necessary to evoke dopamine release through this pathway. The frequency-dependence of disynaptic nicotinic modulation has led to the hypothesis that nAChRs act as a high-pass filter in the dopaminergic microcircuit. Here, we used optogenetics to selectively stimulate either ChIs or dopamine terminals directly in the striatum. To measure the functional consequence of dopamine release, D2-receptor synaptic activity was assessed via virally overexpressed potassium channels (GIRK2) in medium spiny neurons (MSNs). We found that nicotinic-mediated dopamine release was blunted at higher frequencies because nAChRs exhibit prolonged desensitization after a single pulse of synchronous ChI activity. However, when dopamine neurons alone were stimulated, nAChRs had no effect at any frequency. We further assessed how opioid receptors modulate these two mechanisms of release. Bath application of the κ opioid receptor agonist U69593 decreased D2-receptor activation through both pathways, whereas the μ opioid receptor agonist DAMGO decreased D2-receptor activity only as a result of cholinergic-mediated dopamine release. Thus the release of dopamine can be independently modulated when driven by either dopamine neurons or cholinergic interneurons.
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, 44106-4970 USA.
authors.forename: Aphroditi A
authors.initials: AA
authors.lastname: Mamaligas
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, 44106-4970 USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, 44106-4970 USA.|Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, 44106-4970 USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Ford
mesh_terms: D000818:Animals; D059329:Cholinergic Neurons / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism; D051379:Mice; D062308:Optogenetics / Q000379:methods; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*
chemical_list: C000600618:DRD2 protein, mouse; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497069:Kcnj6 protein, mouse; D017448:Receptors, Dopamine D2; D011978:Receptors, Nicotinic; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-