Neural circuit mechanism for learning dependent on dopamine transmission: roles of striatal direct and indirect pathways in sensory discrimination.
The dorsal striatum in basal ganglia circuit mediates learning processes contributing to instrumental motor actions. The striatum receives excitatory inputs from many cortical areas and the thalamic nuclei and dopaminergic inputs from the ventral midbrain and projects to the output nuclei through direct and indirect pathways. The neural mechanism remains unclear as to how these striatofugal pathways control the learning processes of instrumental actions. Here, we addressed the behavioral roles of the two striatofugal pathways in the performance of sensory discrimination by using immunotoxin (IT)-mediated cell targeting. IT targeting of the striatal direct pathway in mutant mice lengthened the response time but did not affect the accuracy of the response selection in visual discrimination. Subregion-specific pathway targeting revealed a delay in motor responses generated by elimination of the direct pathway arising from the dorsomedial striatum (DMS) but not from the dorsolateral striatum (DLS). These findings indicate that the direct pathway, in particular that from the DMS, contributes to the regulation of the response time in visual discrimination. In addition, IT targeting of the striatal indirect pathway originating from the DLS in transgenic rats impaired the accuracy of response selection in auditory discrimination, whereas the response time remained normal. These data demonstrate that the DLS-derived indirect pathway plays an essential role in the control of the selection accuracy of learned motor responses. Our results suggest that striatal direct and indirect pathways act cooperatively to regulate the selection accuracy and response time of learned motor actions in the performance of discriminative learning.
Department of Molecular Genetics, Institute for Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima, Japan. Electronic address: kazuto@fmu.ac.jp.
Kazuto
K
Kobayashi
Ryoji
R
Fukabori
Kayo
K
Nishizawa
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D017072:Neostriatum / Q000502:physiology*; D009435:Synaptic Transmission
D004298:Dopamine
Instrumental learning; Neural circuit; Response selection; Response time; Striatofugal pathway; Transgenic animal