title: Nicotinic receptor subtypes differentially modulate glutamate release in the dorsal medial striatum.
abstract: The dorsal medial striatum is a crucial part of the neural network that subserves dynamic, goal-directed behaviors. Functional output of this nucleus is shaped, in part, by the influence of glutamatergic inputs. Striatal cholinergic systems have the capacity to modulate these excitatory inputs through presynaptic nicotinic acetylcholine receptors (nAChRs); however, the individual contribution of the two major nicotinic receptor subtypes, α4β2 and α7, to such modulation is not well characterized. In the present experiments, glutamate biosensors were used to monitor nAChR-dependent glutamate release with high temporal precision in the dorsal medial striatum of rats. Both α4β2 and α7 nAChRs were found to potently modulate glutamate release; however the two receptor subtypes do so in strikingly different ways. α7 nAChRs appear to enhance release from glutamatergic terminals. In contrast, α4β2 nAChRs act as a brake on glutamate release via an interaction with local dopaminergic inputs and D2 receptors. Combined, the present data reveal the capacity of local striatal cholinergic signaling to dynamically modulate excitatory inputs through nAChRs.
authors: Pfizer, INC, Neuroscience Research Unit, Cambridge, MA 02139, USA. Electronic address: William.howe@pfizer.com.
authors: William M
authors: WM
authors: Howe
authors: Pfizer, INC, Neuroscience Research Unit, Cambridge, MA 02139, USA.
authors: Damon A
authors: DA
authors: Young
authors: Pfizer, INC, Neuroscience Research Unit, Cambridge, MA 02139, USA.
authors: George
authors: G
authors: Bekheet
authors: Pfizer, INC, Neuroscience Research Unit, Cambridge, MA 02139, USA.
authors: Rouba
authors: R
authors: Kozak
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D020318:Rats, Long-Evans; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D011978:Receptors, Nicotinic; D018698:Glutamic Acid; D009538:Nicotine; D000109:Acetylcholine; D004298:Dopamine