A cytoarchitectonic and chemoarchitectonic analysis of the dopamine cell groups in the substantia nigra, ventral tegmental area, and retrorubral field in the mouse

Fu, Yuhong; Yuan, Yuan; Halliday, Glenda M.; Rusznák, Zoltán; Watson, Charles; Paxinos, George

doi:10.1007/s00429-011-0349-2

Cited by 160 publications

(207 citation statements)

References 42 publications

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“…Neurons located in the SNc, the dopaminergic cell population that is particularly vulnerable to degeneration in PD (49), signal movement onset with a pause in firing, whereas more resistant populations (in the VTA and SNL) do not. Alteration of the movement-related firing of SNc neurons and the resultant loss of dopamine signaling in experimental parkinsonism suggest that the activity dynamics we define here are important for the control of voluntary movement.…”

Section: Discussionmentioning

confidence: 99%

Representation of spontaneous movement by dopaminergic neurons is cell-type selective and disrupted in parkinsonism

Dodson

Dreyer

Jennings

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

166

167

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Midbrain dopaminergic neurons are essential for appropriate voluntary movement, as epitomized by the cardinal motor impairments arising in Parkinson's disease. Understanding the basis of such motor control requires understanding how the firing of different types of dopaminergic neuron relates to movement and how this activity is deciphered in target structures such as the striatum. By recording and labeling individual neurons in behaving mice, we show that the representation of brief spontaneous movements in the firing of identified midbrain dopaminergic neurons is cell-type selective. Most dopaminergic neurons in the substantia nigra pars compacta (SNc), but not in ventral tegmental area or substantia nigra pars lateralis, consistently represented the onset of spontaneous movements with a pause in their firing. Computational modeling revealed that the movement-related firing of these dopaminergic neurons can manifest as rapid and robust fluctuations in striatal dopamine concentration and receptor activity. The exact nature of the movement-related signaling in the striatum depended on the type of dopaminergic neuron providing inputs, the striatal region innervated, and the type of dopamine receptor expressed by striatal neurons. Importantly, in aged mice harboring a genetic burden relevant for human Parkinson's disease, the precise movement-related firing of SNc dopaminergic neurons and the resultant striatal dopamine signaling were lost. These data show that distinct dopaminergic cell types differentially encode spontaneous movement and elucidate how dysregulation of their firing in early Parkinsonism can impair their effector circuits.opamine is vital for normal motor function, as exemplified by the motor deficits arising from the dysfunction/degeneration of midbrain dopaminergic neurons in Parkinson's disease (PD). One prevailing view is that midbrain dopaminergic neurons guide purposeful actions through encoding value, for example, by conveying the difference between expected and actual reward (1-3). Although this function has been ascribed to all midbrain dopaminergic neurons, there is considerable functional heterogeneity across different cell populations in the ventral tegmental area (VTA; A10) and the substantia nigra pars compacta (SNc; A9) (4-7). For example, some dopaminergic neurons respond to novel or salient events or during cognitive processes such as decision making and working memory (6,(8)(9)(10). Moreover, although the firing of these dopaminergic neurons generally has been thought not to vary consistently with movement (3, 11), there is evidence that the activity of putatively classified dopaminergic neurons can change during movement execution in a heterogeneous manner (12-16). This evidence, in turn, raises the possibilities that at least some types of movement might be differentially encoded by the firing of distinct populations of dopaminergic neuron and that dysregulation of such activity might contribute to motor impairment in PD before, or commensurate with, frank neurodegeneration.To ...

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Section: Discussionmentioning

confidence: 99%

Representation of spontaneous movement by dopaminergic neurons is cell-type selective and disrupted in parkinsonism

Dodson

Dreyer

Jennings

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

166

167

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“…Because this issue is beyond the scope of this article, this will not be addressed here. However, more information can be found elsewhere (Gonzá-lez-Hernández and Rodríguez 2000; Fu et al 2012). In humans, dopaminergic neurons located in the SNc contain the dopamine precursor www.perspectivesinmedicine.org neuromelanin, a pigment that produces the black color inherent to SNc territories as seen in freshly extracted brains in human necropsies.…”

Section: Substantia Nigra Pars Compactamentioning

confidence: 99%

Functional Neuroanatomy of the Basal Ganglia

Lanciego

Luquin

Obeso

2012

Cold Spring Harbor Perspectives in Medicine

641

474

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The "basal ganglia" refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amplified with the emergence of new data. Furthermore, parallel circuits subserve the other functions of the basal ganglia engaging associative and limbic territories. Disruption of the basal ganglia network forms the basis for several movement disorders. This article provides a comprehensive account of basal ganglia functional anatomy and chemistry and the major pathophysiological changes underlying disorders of movement. We try to answer three key questions related to the basal ganglia, as follows: What are the basal ganglia? What are they made of? How do they work? Some insight on the canonical basal ganglia model is provided, together with a selection of paradoxes and some views over the horizon in the field.T he basal ganglia and related nuclei consist of a variety of subcortical cell groups engaged primarily in motor control, together with a wider variety of roles such as motor learning, executive functions and behavior, and emotions. The term basal ganglia in the strictest sense refers to nuclei embedded deep in the brain hemispheres (striatum or caudate-putamen and globus pallidus), whereas related nuclei consist of structures located in the diencephalon (subthalamic nucleus), mesencephalon (substantia nigra), and pons ( pedunculopontine nucleus). Ideas and concepts regarding the functions of the basal ganglia were strongly influenced by clinical observations during the 20th century, which showed that lesions of the lenticular nucleus ( putamen and globus pallidus) and the subthalamic nucleus (STN) were associated with parkinsonian signs, dystonia, and hemiballismus (Wilson 1925;Purdon-Martin 1927). Thus, the terms extra-pyramidal system and extra-pyramidal syndrome were frequently used in the past to refer to the pathological basis of movement disorders in an attempt to make a clear distinction from the pyramidal system (corticofugal neurons that give rise to corticospinal projections). At present, these terms and distinctions are considered obsolete and misleading and, therefore, will not be used in

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“…Ϫ VTA and dorsomedial SNc DA neurons (Liang et al, 1996;Fu et al, 2012;Luk et al, 2013), and KCND3 (also known as Kv4.3), an A-type potassium channel subunit expressed in mature SNc DA neurons (Serô dio and Rudy, 1998;Liss et al, 2001) to discriminate at least between these two neuronal subsets among the in vitro-differentiated (iPSC-derived) mdDA neurons. The treatment of differentiating Pitx3 GFP/ϩ iPSC tf s with CHIR99, DKK3, and/or WNT1 led to a significant decrease (by ϳ51%) of the proportion of TH ϩ neurons coexpressing CALB1 (Fig.…”

Section: Combined Dkk3/wnt1 Treatment Generates the Highest Proportiomentioning

confidence: 99%

“…Remarkably, the treatment with WNT/␤-catenin signaling factors generally decreased the proportion of TH ϩ cells coexpressing the predominant VTA DA neuron marker CALB1 (Di Salvio et al, 2010a;Fu et al, 2012) and increased the proportion of TH ϩ cells coexpressing KCND3, a molecular marker of SNc DA neurons (Serô dio and Rudy, 1998;Liss et al, 2001). Therefore, our data support the idea that WNT/␤-catenin signaling is particularly important, at least in the mouse, for the generation of a rostrolateral (PBP and dorsomedial SNc) mdDA neuronal subpopulation in vivo and in vitro.…”

mentioning

confidence: 99%

Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic Neuronal SubsetIn Vivoand from Pluripotent Stem CellsIn Vitroin the Mouse

Fukusumi¹,

Meier²,

Götz³

et al. 2015

J. Neurosci.

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Wingless-related MMTV integration site 1 (WNT1)/␤-catenin signaling plays a crucial role in the generation Significance StatementWe show here that Dickkopf 3 (DKK3), a secreted modulator of WNT (Wingless-related MMTV integration site)/␤-catenin signaling, is both necessary and sufficient for the proper differentiation and survival of a rostrolateral (parabrachial pigmented nucleus and dorsomedial substantia nigra pars compacta) mesodiencephalic dopaminergic neuron subset, using Dkk3 mutant mice and murine primary ventral midbrain and pluripotent stem cells. The progressive loss of these dopamine-producing mesodiencephalic neurons is a hallmark of human Parkinson's disease, which can up to now not be halted by clinical treatments of this disease. Thus, the soluble DKK3 protein might be a promising new agent for the improvement of current protocols for the directed differentiation of pluripotent and multipotent stem cells into mesodiencephalic dopaminergic neurons and for the promotion of their survival in situ.

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A cytoarchitectonic and chemoarchitectonic analysis of the dopamine cell groups in the substantia nigra, ventral tegmental area, and retrorubral field in the mouse

Cited by 160 publications

References 42 publications

Representation of spontaneous movement by dopaminergic neurons is cell-type selective and disrupted in parkinsonism

Representation of spontaneous movement by dopaminergic neurons is cell-type selective and disrupted in parkinsonism

Functional Neuroanatomy of the Basal Ganglia

Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic Neuronal SubsetIn Vivoand from Pluripotent Stem CellsIn Vitroin the Mouse

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