Studies of the ventral striatum and its connections are of key importance for understanding the neurobiology of drug abuse and mental disorders. Anatomical, physiological and pharmacological studies in these brain regions have been central in gaining insight into the mechanisms underlying motivation, reward, and goal-directed behaviors. The """"""""motive"""""""" or drug-reward circuit involves the orbital and medial prefrontal cortex (OMPFC), the ventral striatum (VS), the ventral pallidum/substantia nigra, pars reticulata (VP/SNr), and the medial dorsal N. of the thalamus (MD), which links the circuit back to cortex. The opiates and excitatory amino acids through their interactions with ventral striatal transmitters and receptors, are central to studies on goal-directed behaviors, drug addiction, and behavioral disorders. During the previous funding period we identified important components of this circuit in primates along with the histochemical organization of the ventral striatal shell/core sub-territories. Using retrograde tracer injections, we demonstrated the OMPFC and thalamic projections to the VS. Based on these studies, the region of the striatum that can be associated with goal directed behaviors appears to be extensive. Furthermore, we demonstrated an integrative network of connections via the midbrain. The next step is to link together these components. The experiments proposed here will test the hypothesis that the ventral cortical- basal ganglia-cortical pathways via the thalamus and substantia nigra are also governed by an integrative network of connections with information flowing from limbic to more associative cortical regions in a step-wise manner through the ventral striatum. The experiments will first use anterograde tracer injections to delineate the rostro-caudal extent of the OMPFC projection fields to the VS, their relationship to the VS shell/core sub-territories and to the distribution of the mu receptor and GluR1 sub-unit receptor subtype. These experiments will also examine the relationship between MD and midline thalamic projections to the shell/core regions, how these relate to OMPFC inputs, and the mu and GluR1 receptors. A final set of experiments will address the connections between the output pathways from specific shell/core regions to the VP/SNr to the MD nucleus. These studies will link together how the OMPFC and thalamic inputs to the VS are related to the shell and core sub-territories, and the mu and GluR1 receptors and follow the outputs via the VP/SNr to the MD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022511-14
Application #
6539635
Study Section
Special Emphasis Panel (ZRG1-IFCN-1 (01))
Program Officer
Oliver, Eugene J
Project Start
1985-07-01
Project End
2005-06-30
Budget Start
2002-07-01
Budget End
2005-06-30
Support Year
14
Fiscal Year
2002
Total Cost
$301,827
Indirect Cost
Name
University of Rochester
Department
Neurosciences
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Haber, Suzanne N; Calzavara, Roberta (2009) The cortico-basal ganglia integrative network: the role of the thalamus. Brain Res Bull 78:69-74
Fudge, J L; Kunishio, K; Walsh, P et al. (2002) Amygdaloid projections to ventromedial striatal subterritories in the primate. Neuroscience 110:257-75
McFarland, Nikolaus R; Haber, Suzanne N (2002) Thalamic relay nuclei of the basal ganglia form both reciprocal and nonreciprocal cortical connections, linking multiple frontal cortical areas. J Neurosci 22:8117-32
Haber, S; McFarland, N R (2001) The place of the thalamus in frontal cortical-basal ganglia circuits. Neuroscientist 7:315-24
McFarland, N R; Haber, S N (2001) Organization of thalamostriatal terminals from the ventral motor nuclei in the macaque. J Comp Neurol 429:321-36
McFarland, N R; Haber, S N (2000) Convergent inputs from thalamic motor nuclei and frontal cortical areas to the dorsal striatum in the primate. J Neurosci 20:3798-813
Haber, S N; Fudge, J L; McFarland, N R (2000) Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum. J Neurosci 20:2369-82
Song, D D; Haber, S N (2000) Striatal responses to partial dopaminergic lesion: evidence for compensatory sprouting. J Neurosci 20:5102-14
Haber, S N; McFarland, N R (1999) The concept of the ventral striatum in nonhuman primates. Ann N Y Acad Sci 877:33-48
Chikama, M; McFarland, N R; Amaral, D G et al. (1997) Insular cortical projections to functional regions of the striatum correlate with cortical cytoarchitectonic organization in the primate. J Neurosci 17:9686-705

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