Loss of functional specificity in the dorsal striatum of chronic cocaine users
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ABSTRACT The division of the striatum into dorsal and ventral districts is of central clinical importance. The dorsal striatum is differentially affected in Huntington’s disease, dopamine in the ventral striatum is differentially spared in Parkinson’s disease, and human brain imaging studies implicate the ventral striatum in addictive disorders. If fits that the dorsal striatum contains the cells of origin of the direct and indirect basal ganglia pathways for motor control. The ventral striatum is a node in neural circuits related to motivation and affect. Despite these striking neurobiologic contrasts, there is almost no information about how the dorsal and ventral divisions of the striatum are set up during development. Here, we demonstrate that interactions between the two key transcription factors Nolz-1 and Dlx1/2 control the migratory paths of developing striatal neurons to the dorsal or ventral striatum. Moreover, these same transcription factors control the cell identity of striatal projection neurons in both the dorsal and ventral striatum including the cell origin of the direct and indirect pathways. We show that Nolz-1 suppresses Dlx1/2 expression. Deletion of Nolz-1 or over-expression of Dlx1/2 can produce a striatal phenotype characterized by withered dorsal striatum and a swollen ventral striatum, and that we can rescue this phenotype by manipulating the interactions between Nolz-1 and Dlx1/2 transcription factors. This evidence suggests that the fundamental basis for divisions of the striatum known to be differentially vulnerable at maturity is already encoded by the time embryonic striatal neurons begin their migrations into the developing striatum.
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The striatal complex of basal ganglia comprises two functionally distinct districts. The dorsal district controls motor and cognitive functions. The ventral district regulates the limbic function of motivation, reward, and emotion. The dorsoventral parcellation of the striatum also is of clinical importance as differential striatal pathophysiologies occur in Huntington's disease, Parkinson's disease, and drug addiction disorders. Despite these striking neurobiologic contrasts, it is largely unknown how the dorsal and ventral divisions of the striatum are set up. Here, we demonstrate that interactions between the two key transcription factors Nolz-1 and Dlx1/2 control the migratory paths of striatal neurons to the dorsal or ventral striatum. Moreover, these same transcription factors control the cell identity of striatal projection neurons in both the dorsal and the ventral striata including the D1-direct and D2-indirect pathways. We show that Nolz-1, through the I12b enhancer, represses Dlx1/2, allowing normal migration of striatal neurons to dorsal and ventral locations. We demonstrate that deletion, up-regulation, and down-regulation of Nolz-1 and Dlx1/2 can produce a striatal phenotype characterized by a withered dorsal striatum and an enlarged ventral striatum and that we can rescue this phenotype by manipulating the interactions between Nolz-1 and Dlx1/2 transcription factors. Our study indicates that the two-tier system of striatal complex is built by coupling of cell-type identity and migration and suggests that the fundamental basis for divisions of the striatum known to be differentially vulnerable at maturity is already encoded by the time embryonic striatal neurons begin their migrations into developing striata.
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Mapping structural spatial change (i.e., gradients) in the striatum is essential for understanding the function of the basal ganglia in both health and disease. We developed a method to identify and quantify gradients of microstructure in the single human brain in vivo. We found spatial gradients in the putamen and caudate nucleus of the striatum that were robust across individuals, clinical conditions, and datasets. By exploiting multiparametric quantitative MRI, we found distinct, spatially dependent, aging-related alterations in water content and iron concentration. Furthermore, we found cortico-striatal microstructural covariation, showing relations between striatal structural gradients and cortical hierarchy. In Parkinson’s disease (PD) patients, we found abnormal gradients in the putamen, revealing changes in the posterior putamen that explain patients’ dopaminergic loss and motor dysfunction. Our work provides a noninvasive approach for studying the spatially varying, structure-function relationship in the striatum in vivo, in normal aging and PD.
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This chapter contains section titled: Chemical Morphology of the Striatum Functional Studies of Neurotransmitters in the Striatum Parallel Organization of the Mesolimbic DA Neurons in Ventral Striatum The Importance of Dopamine Innervation of the Striatum References Discussion References
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OBJECTIVE: To demonstrate the existence of the marginal division in human stritum. METHODS: The cytoar-chitecture and distribution of the neurotransmitters in human fetal striatum were studied using Nissl staining and immuno-cytochemistry. RESULTS: In the sections with Nissl staining, a distinct fusiform cell zone was observed between the putamen and the globus pallidus of the human striatum. The long axes of these neurons in this region stretched dorsoventrally in parallel with the border between the putamen and the globus pallidus. Numerous L-ENK-, NT-, SOM-and SP-positive fibers and a few L-ENK-and NT-positive cells were found in the marginal division. CONCLUSION: For the first time we demonstrate that human also have the marginal division in the striatum which is similar to that of the mammals as the rats, cats and monkeys
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Abstract Parkinson's disease (PD) is a neurodegenerative disorder associated with the striatum. Previous studies indicated that subdivisions of the striatum with distinct functional connectivity profiles contribute to different pathogeneses in PD. Segregated structural covariance (SC) pattern between the striatum and neocortex observed in healthy subjects, however, remain unknown in PD. The purpose of this study is to map and compare the subregional striatal SC network organization between 30 healthy controls and 48 PD patients and to investigate their association with the disease severity. The striatal SC network was statistically inferred by correlating the mean gray matter (GM) volume of six striatal subdivisions (including the bilateral dorsal caudate, superior ventral striatum, inferior ventral striatum, dorsal caudal putamen, dorsal rostral putamen, and ventral rostral putamen) with the entire neocortical GM volume in voxel‐wise manner. The PD patients revealed marked atrophy in the striatum, cerebellum, and extra‐striatum neocortices. As predicted, segregated striatal SC network patterns were observed in both groups. This suggests that in PD, pathological processes occurring in the striatum affect the same striato‐cortical networks that covary with the striatum in healthy brains. The PD patients further demonstrated atypical striatal SC patterns between the caudate, parahippocampus temporal cortices, and cerebellum, which corresponded to dopaminergic associated network. The areas with significant group differences in SC were further associated with disease severity. Our findings support previous studies indicating that PD is associated with altered striato‐cortical networks, and suggest that structural changes in the striatum may result in a cascade of alterations in multiple neocortices. Hum Brain Mapp 36:1567–1584, 2015 . © 2014 Wiley Periodicals, Inc .
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The striatum is the input component of the basal ganglia from the cerebral cortex. It includes the caudate, putamen, and nucleus accumbens. Thus, the striatum is an important component in limbic frontal-subcortical circuitry and is believed to be relevant both for reward-guided behaviors and for the expression of psychosis. The dorsal striatum is composed of the caudate and putamen, both of which are further subdivided into pre- and post-commissural components. The ventral striatum (VS) is primarily composed of the nucleus accumbens. The striatum can be functionally divided into three broad regions: 1) a limbic; 2) a cognitive and 3) a sensor-motor region. The approximate corresponding anatomic subregions for these 3 functional regions are: 1) the VS; 2) the pre/post-commissural caudate and the pre-commissural putamen and 3) the post-commissural putamen. We believe assessing these subregions, separately, in disorders with limbic and cognitive impairment such as schizophrenia may yield more informative group differences in comparison with normal controls than prior parcellation strategies of the striatum such as assessing the caudate and putamen. The manual parcellation of the striatum into these subregions is currently defined using certain landmark points and geometric rules. Since identification of these areas is important to clinical research, a reliable and fast parcellation technique is required. Currently, only full manual parcellation using editing software is available; however, this technique is extremely time intensive. Previous work has shown successful application of heuristic rules into a semi-automatic platform1. We present here a semi-automatic algorithm which implements the rules currently used for manual parcellation of the striatum, but requires minimal user input and significantly reduces the time required for parcellation.
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The concept of the ventral striatum was first put forth by Heimer and Wilson to describe the extension of basal ganglia elements into the olfactory tubercle. The ventral striatum includes the conventional nucleus accumbens, which has been closely associated with reward and motivation. This paper uses the afferent connections to the ventral striatum to define this region in monkeys. Furthermore the shell and core subterritories are discussed with respect to their histochemistry and specific connections.
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