title: Metabotropic glutamate receptor 4-immunopositive terminals of medium-sized spiny neurons selectively form synapses with cholinergic interneurons in the rat neostriatum.
abstract: Metabotropic glutamate receptor 4 (mGluR4) is localized mainly to presynaptic membranes in the brain. Rat neostriatum has been reported to contain two types of mGluR4-immunoreactive axon varicosities: small, weakly immunoreactive varicosities that were distributed randomly (type 1) and large, intensely immunoreactive ones that were often aligned linearly (type 2). In the present study, most type 1 terminals formed asymmetric synapses on dendritic spines, whereas type 2 terminals made symmetric synapses on dendritic shafts, showing immunoreactivity for GABAergic markers. After depletion of neostriatal neurons, type 2 but not type 1 varicosities were largely decreased in the damaged region. When medium-sized spiny neurons (MSNs) were labeled with Sindbis virus expressing membrane-targeted green fluorescent protein, mGluR4 immunoreactivity was observed on some varicosities of their axon collaterals in immunofluorescence and immunoelectron microscopies. Furthermore, type 2 varicosities were often positive for substance P but mostly negative for striatal interneuron markers and preproenkephalin. Thus, striatonigral/striato-entopeduncular MSNs are likely to be the largest source of type 2 mGluR4-immunopositive axon terminals in the neostriatum. Next, in the double-immunofluorescence study, almost all choline acetyltransferase (ChAT)-immunopositive and 41% of NK1 receptor-positive dendrites were heavily associated with type 2 mGluR4-immunoreactive varicosities. Neuronal nitric oxide synthase (nNOS)-positive dendrites, in contrast, seemed associated with only a few type 2 varicosities. Conversely, almost all type 2 varicosities were closely apposed to NK1 receptor-positive dendrites that were known to be derived from cholinergic and nNOS-producing interneurons. These findings indicate that the mGluR4-positive terminals of MSN axon collaterals selectively form synapses with neostriatal cholinergic interneurons.
authors.affiliation: Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Kuramoto
authors.forename: Fumino
authors.initials: F
authors.lastname: Fujiyama
authors.forename: Tomo
authors.initials: T
authors.lastname: Unzai
authors.forename: Kouichi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hioki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Furuta
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shigemoto
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraguti
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism* / Q000648:ultrastructure; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000201:enzymology* / Q000648:ultrastructure; D009434:Neural Pathways / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D018094:Receptors, Metabotropic Glutamate; D002795:Choline O-Acetyltransferase; C108823:metabotropic glutamate receptor 4