Active intermixing of indirect and direct neurons builds the striatal mosaic

Tinterri, Andrea; Mendary, Fabien; Diana, Marco A.; Lokmane, Ludmilla; Keita, Maryama; Coulpier, Fanny; Lemoine, Sophie; Mailhes, Caroline; Mathieu, Benjamin; Marchan-Sala, Paloma; Campbell, Kenneth; Győry, Ildikó; Grosschedl, Rudolf; Popa, Daniela; Garel, Sonia

doi:10.1101/378372

Cited by 8 publications

(16 citation statements)

References 107 publications

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“…We therefore propose that D1/D2-SPNs provide a key balance necessary for proper striatal functioning. This balance between D1/D2-, D1-, and D2-SPNs is likely formed during embryonic stages and matures during early postnatal development, following a stage where more SPNs co-express both D1R and D2R [43][44][45] . Only a fraction of SPNs in the indirect pathway will conserve expression of both D1R and D2R, whereas most express only D2R, and all SPNs in the direct pathway express only D1R.…”

Section: Discussionmentioning

confidence: 99%

Unexpected contributions of striatal projection neurons coexpressing dopamine D1 and D2 receptors in balancing motor control

Bonnavion

Varin

Fakhfouri

et al. 2022

Preprint

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The central function of the striatum and its dopaminergic (DA) afference in motor control and integration of cognitive and emotional processes is commonly explained by the two striatal efferent pathways characterized by striatal projection neurons (SPNs) expressing DA D1 receptor- and D2 receptor (D1-SPNs and D2-SPNs), respectively, regardless of SPNs co-expressing these two receptors (D1/D2-SPNs). Here, after developing an approach that enables to target these hybrid SPNs, we demonstrated that, although these SPNs are rare, they play a major role in guiding the motor function of the other two main populations and convey a DA-mediated antagonistic motor brake. D1/D2-SPNs project exclusively to the external globus pallidus (GPe) and have specific electrophysiological features with distinctive integration of DA signals. Optogenetic stimulation and loss-of-function experiments indicated that D1/D2-SPNs potentiate the prokinetic and antikinetic functions of D1-SPNs and D2-SPNs, respectively, and restrain the integrated motor response to psychostimulants. Overall, our findings demonstrate the essential role of this third unacknowledged population of D1/D2 co-expressing neurons, which orchestrates the fine-tuning of DA regulation in the thalamo-cortico-striatal loops.One-Sentence SummaryD1/D2 striatal output promotes dopamine-induced motor inhibition

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Section: Discussionmentioning

confidence: 99%

Unexpected contributions of striatal projection neurons coexpressing dopamine D1 and D2 receptors in balancing motor control

Bonnavion

Varin

Fakhfouri

et al. 2022

Preprint

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“…Ebf1 is expressed in the lateral ganglionic eminence (LGE), which generates striatal projection neurons, including medium spiny neurons that are preferential lost in Huntington's disease (49,50). Ebf1 is essential for striatum formation and the generation of direct striatal projection neurons that project to the substantia nigra (51,52). Functional experiments are necessary to determine the potential impact of this and other non-coding polymorphisms on ASH1L transcription.…”

Section: Discussionmentioning

confidence: 99%

Using Genomic Resources for Linkage Analysis in Peromyscus with an Application for Characterizing Dominant Spot

Shang

Horovitz

McKenzie

et al. 2020

Preprint

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Background: Peromyscus are the most common mammalian species in North America and are widely used in both laboratory and field studies. The deer mouse, P. maniculatus and the old-field mouse, P. polionotus, are closely related and can generate viable and fertile hybrid offspring. The ability to generate hybrid offspring, coupled with developing genomic resources, enables researchers to conduct linkage analysis studies to identify genomic loci associated with specific traits. Results: We used available genomic data to identify DNA polymorphisms between P. maniculatus and P. polionotus and used the polymorphic data to identify the range of genetic complexity that underlies physiological and behavioral differences between the species, including cholesterol metabolism and genes associated with autism. In addition, we used the polymorphic data to conduct a candidate gene linkage analysis for the Dominant spot trait and determined that Dominant spot is linked to a region of chromosome 20 that contains a strong candidate gene, Sox10. During the linkage analysis, we found that the spot size varied quantitively in affected Peromyscus based on genetic background. Conclusions: The expanding genomic resources for Peromyscus facilitate their use in linkage analysis studies, enabling the identification of loci associated with specific traits. More specifically, we have linked a coat color spotting phenotype, Dominant spot, with Sox10, a member the neural crest gene regulatory network, and that there are likely two genetic modifiers that interact with Dominant spot. These results establish Peromyscus as a model system for identifying new alleles of the neural crest gene regulatory network.

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“…Ebf1 is expressed in the lateral ganglionic eminence (LGE), which generates striatal projection neurons, including medium spiny neurons that are preferential lost in Huntington's disease [48,49]. Ebf1 is essential for striatum formation and the generation of direct striatal projection neurons that project to the substantia nigra [50,51]. Functional experiments are necessary to determine the potential impact of this and other non-coding polymorphisms on ASH1L transcription.…”

Section: Discussionmentioning

confidence: 99%

Using genomic resources for linkage analysis in Peromyscus with an application for characterizing Dominant Spot

et al. 2020

View full text Add to dashboard Cite

Background Peromyscus are the most common mammalian species in North America and are widely used in both laboratory and field studies. The deer mouse, P. maniculatus and the old-field mouse, P. polionotus, are closely related and can generate viable and fertile hybrid offspring. The ability to generate hybrid offspring, coupled with developing genomic resources, enables researchers to conduct linkage analysis studies to identify genomic loci associated with specific traits. Results We used available genomic data to identify DNA polymorphisms between P. maniculatus and P. polionotus and used the polymorphic data to identify the range of genetic complexity that underlies physiological and behavioral differences between the species, including cholesterol metabolism and genes associated with autism. In addition, we used the polymorphic data to conduct a candidate gene linkage analysis for the Dominant spot trait and determined that Dominant spot is linked to a region of chromosome 20 that contains a strong candidate gene, Sox10. During the linkage analysis, we found that the spot size varied quantitively in affected Peromyscus based on genetic background. Conclusions The expanding genomic resources for Peromyscus facilitate their use in linkage analysis studies, enabling the identification of loci associated with specific traits. More specifically, we have linked a coat color spotting phenotype, Dominant spot, with Sox10, a member the neural crest gene regulatory network, and that there are likely two genetic modifiers that interact with Dominant spot. These results establish Peromyscus as a model system for identifying new alleles of the neural crest gene regulatory network.

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Active intermixing of indirect and direct neurons builds the striatal mosaic

Cited by 8 publications

References 107 publications

Unexpected contributions of striatal projection neurons coexpressing dopamine D1 and D2 receptors in balancing motor control

Unexpected contributions of striatal projection neurons coexpressing dopamine D1 and D2 receptors in balancing motor control

Using Genomic Resources for Linkage Analysis in Peromyscus with an Application for Characterizing Dominant Spot

Using genomic resources for linkage analysis in Peromyscus with an application for characterizing Dominant Spot

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