Our previous work in rats suggests that cortical neurons projecting to brainstem premotor cell groups and spinal cord via the pyramidal tract (PT-type) preferentially target striatal neurons projecting to the external pallidal segment (GPe), while cortical neurons having only intratelencephalic projections (IT- type) preferentially target striatal neurons projecting to the internal pallidal segment (GPi) and/or the substantia nigra pars reticulata (SNr). These findings suggest that PT-type corticostriatal neurons may provide striato-GPe neurons with information about cortical motor commands needed for their role in suppressing potentially conflicting movements, while integration of IT-type input from diverse cortical areas may be required for striato-GPi/SNr neurons to play their role in initiating desired movement. Synaptic facilitation or disfacilitation of subsets of these inputs could play a role in motor learning. Our conclusions about differential cortical inputs to the two main types of striatal projection neurons are, however, based on preferential but not exclusive labeling of striatal neuron types. Moreover, we did not distinguish between striato-GPi and striato-SNr neurons in these prior studies. Thus, the extent to which each of the three main types of striatal projection neurons in rats receive input from more than one type of cortical neuron remains uncertain. Additionally, we also do now know if our findings for rats are true for primates, and thus clinically relevant to the human basal ganglia.
In Aim 1 of the current proposal, we will use in vivo intracellular methods in rats to record from individual striatal projection neurons and then at the end of the physiology session identify their type by biocytin-filling the neuron (and later tracing the axon of each to its destination). For each neuron we will use electrophysiological and LM/EM anatomical methods, so as to characterize the extent of the specificity of the IT input for striato-GPi/SNr neurons and the PT input for striato-GPe neurons.
In Aims 2 and 3, we will determine by dextran amine labeling, immunolabeling and EM analysis if IT-type terminals preferentially target striato-GPi and striato-SNr neurons while PT-type terminals preferentially target striato-GPe neurons in monkeys. Given the critical roles of the cortical input to striatum in providing an instructive signal to the striatum and in the plasticity underlying motor learning, our studies will: 1) help reveal how the striato-GPi/SNr and striato-GPe neurons play complementary roles in motor control;2) help clarify the mechanisms underlying the role of the basal ganglia in movement initiation and in the execution of movement sequences;and 3) help explain the relationship between the role of the basal ganglia in motor learning and in motor performance.

Public Health Relevance

This study will clarify which neurons of cerebral cortex communicate with each of the two circuits of the basal ganglia, one of which facilitates desired movements and the other suppresses unwanted movements. The findings will clarify how the information provided by cerebral cortex enables the basal ganglia to play its role in movement control and in the learning of new motor routines. The findings will suggest new insights into the role of abnormalities in the cortical input to striatum in Huntington's disease, Parkinson's disease, Tourette Syndrome, and obsessive-compulsive disorder, and thereby suggest new therapeutic approaches for treating these disorders.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Sutherland, Margaret L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Tennessee Health Science Center
Anatomy/Cell Biology
Schools of Medicine
United States
Zip Code
Bruce, Laura L; Erichsen, Jonathan T; Reiner, Anton (2016) Neurochemical compartmentalization within the pigeon basal ganglia. J Chem Neuroanat 78:65-86
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
Deng, Yunping; Lanciego, Jose; Goff, Lydia Kerkerian-Le et al. (2015) Differential organization of cortical inputs to striatal projection neurons of the matrix compartment in rats. Front Syst Neurosci 9:51
Deng, Y P; Wong, T; Bricker-Anthony, C et al. (2013) Loss of corticostriatal and thalamostriatal synaptic terminals precedes striatal projection neuron pathology in heterozygous Q140 Huntington's disease mice. Neurobiol Dis 60:89-107
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
LeDoux, Mark S (2012) Exome sequencing for gene discovery: time does not stand still. Ann Neurol 72:628-9
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
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
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
Deng, Yun-Ping; Shelby, Evan; Reiner, Anton J (2010) Immunohistochemical localization of AMPA-type glutamate receptor subunits in the striatum of rhesus monkey. Brain Res 1344:104-23

Showing the most recent 10 out of 11 publications