Recent models of basal ganglia organization have dichotomized striatal projection neurons into two types: 1) neurons containing substance P (SP) that are rich in D1 type dopamine receptors and play a role in promoting desired movement; and 2) neurons that contain enkephalin (ENK) that are rich in D2 type dopamine receptors and play a role in suppressing unwanted movements. We believe that the dichotomy of striatal projection neurons into two major types may be inadequate and we believe the means by which the cortex might differentially control the different types of striatal projection neurons is unresolved. We propose studies to address these issues. First, single-cell RT-PCR in young rats indicates that at least 20 percent of striatal projection neurons co-contain SP and ENK and are functionally distinct in their dopamine and glutamate receptor characteristics. While the precise identity of the SP/ENK population is uncertain, available data suggest that the SP/ENK neurons may primarily include striatal neurons projecting to substantia nigra pars reticulata and/or pars compacta.
Our first aim will use a combination of single-cell RT-PCR, double-label in situ hybridization histochemistry, and retrograde neuronal labeling to determine the phenotypic traits (dynorphin, neurotensin, calbindin and mu opiate receptor content), abundance, distribution, projections, age-related stability, and interphyletic stability of the SP/ENK population relative to the SP-only and ENK-only populations. We will also determine if the SP/ENK neurons in mice and monkeys are typically rich in both D1 and D2 receptors, as appears to be the case in rats. Secondly, we will explore the possibility that the different types of striatal projection neurons carry different signals related to movement control because they receive inputs from different cortical neuron types and/or different cortical regions. To address this issue, we will combine selective anterograde labeling of different types of corticostriatal input and retrograde or intracellular labeling of specific striatal projection neuron types to determine by dual label ultrastructural methods if striatal projection neuron types differ in the inputs they receive from either: 1) the two major types of corticostriatal projection neuron (pyramidal tract versus nonpyramidal tract); or 2) somatosensory cortex versus motor cortex. Our studies will provide insight into normal basal ganglia function and potentially into the cellular bases of diseases of basal ganglia (e.g. Huntington's and Parkinson's disease), which may in turn make it possible to devise more effective preventive and therapeutic measures for such disorders.

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National Institute of Neurological Disorders and Stroke (NINDS)
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Special Emphasis Panel (ZRG1-IFCN-5 (01))
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Edwards, Emmeline
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University of Tennessee Health Science Center
Anatomy/Cell Biology
Schools of Medicine
United States
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Reiner, Anton; Deng, Yun-Ping (2018) Disrupted striatal neuron inputs and outputs in Huntington's disease. CNS Neurosci Ther 24:250-280
Deng, Yun-Ping; Reiner, Anton (2016) Cholinergic interneurons in the Q140 knockin mouse model of Huntington's disease: Reductions in dendritic branching and thalamostriatal input. J Comp Neurol 524:3518-3529
Bruce, Laura L; Erichsen, Jonathan T; Reiner, Anton (2016) Neurochemical compartmentalization within the pigeon basal ganglia. J Chem Neuroanat 78:65-86
Reiner, Anton (2013) You are who you talk with--a commentary on Dugas-Ford et al. PNAS, 2012. Brain Behav Evol 81:146-9
Lei, Wanlong; Deng, Yunping; Liu, Bingbing et al. (2013) Confocal laser scanning microscopy and ultrastructural study of VGLUT2 thalamic input to striatal projection neurons in rats. J Comp Neurol 521:1354-77
Reiner, Anton; Dragatsis, Ioannis; Dietrich, Paula (2011) Genetics and neuropathology of Huntington's disease. Int Rev Neurobiol 98:325-72
Mu, Shuhua; OuYang, Lisi; Liu, Bingbing et al. (2011) Preferential interneuron survival in the transition zone of 3-NP-induced striatal injury in rats. J Neurosci Res 89:744-54
Kuenzel, Wayne J; Medina, Loreta; Csillag, Andras et al. (2011) The avian subpallium: new insights into structural and functional subdivisions occupying the lateral subpallial wall and their embryological origins. Brain Res 1424:67-101
Butler, Ann B; Reiner, Anton; Karten, Harvey J (2011) Evolution of the amniote pallium and the origins of mammalian neocortex. Ann N Y Acad Sci 1225:14-27
Reiner, Anton; Yang, Mao; Cagle, Michael C et al. (2011) Localization of cerebellin-2 in late embryonic chicken brain: implications for a role in synapse formation and for brain evolution. J Comp Neurol 519:2225-51

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