title: Striatal indirect pathway contributes to selection accuracy of learned motor actions.
abstract: The dorsal striatum, which contains the dorsolateral striatum (DLS) and dorsomedial striatum (DMS), integrates the acquisition and implementation of instrumental learning in cooperation with the nucleus accumbens (NAc). The dorsal striatum regulates the basal ganglia circuitry through direct and indirect pathways. The mechanism by which these pathways mediate the learning processes of instrumental actions remains unclear. We investigated how the striatal indirect (striatopallidal) pathway arising from the DLS contributes to the performance of conditional discrimination. Immunotoxin targeting of the striatal neuronal type containing dopamine D(2) receptor in the DLS of transgenic rats resulted in selective, efficient elimination of the striatopallidal pathway. This elimination impaired the accuracy of response selection in a two-choice reaction time task dependent on different auditory stimuli. The impaired response selection was elicited early in the test sessions and was gradually restored as the sessions continued. The restoration from the deficits in auditory discrimination was prevented by excitotoxic lesion of the NAc but not by that of the DMS. In addition, lesion of the DLS mimicked the behavioral consequence of the striatopallidal removal at the early stage of test sessions of discriminative performance. Our results demonstrate that the DLS-derived striatopallidal pathway plays an essential role in the execution of conditional discrimination, showing its contribution to the control of selection accuracy of learned motor responses. The results also suggest the presence of a mechanism that compensates for the learning deficits during the repetitive sessions, at least partly, demanding accumbal function.
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Nishizawa
authors.forename: Ryoji
authors.initials: R
authors.lastname: Fukabori
authors.forename: Kana
authors.initials: K
authors.lastname: Okada
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kai
authors.forename: Motokazu
authors.initials: M
authors.lastname: Uchigashima
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Akira
authors.initials: A
authors.lastname: Shiota
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Ueda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tsutsui
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D001710:Biotin / Q000031:analogs & derivatives; D064032:Calbindin 2; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000166:cytology / Q000293:injuries / Q000502:physiology*; D003911:Dextrans; D004192:Discrimination, Psychological / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000187:drug effects; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D007051:Ibotenic Acid / Q000633:toxicity; D000922:Immunotoxins / Q000633:toxicity; D007395:Interneurons / Q000378:metabolism; D008297:Male; D009042:Motivation / Q000187:drug effects / Q000235:genetics; D009043:Motor Activity / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000172:deficiency / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics; D012055:Reinforcement Schedule; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: D064032:Calbindin 2; D003911:Dextrans; D004745:Enkephalins; D000922:Immunotoxins; D010320:Parvalbumins; D011498:Protein Precursors; D017448:Receptors, Dopamine D2; D015375:Receptors, Interleukin-2; D064030:S100 Calcium Binding Protein G; D015320:Tachykinins; C076397:biotinylated dextran amine; C044206:preprotachykinin; D007051:Ibotenic Acid; D001710:Biotin; C033660:preproenkephalin; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D010751:Phosphopyruvate Hydratase