Integrative multi-dimensional characterization of striatal projection neuron heterogeneity in adult brain

Gayden, Jenesis; Puig, Stéphanie; Srinivasan, Chaitanya; Buck, Silas A.; Gamble, Mackenzie C.; Glausier, Jill R.; Tejeda, Hugo A.; Dong, Yan; Pfenning, Andreas; Logan, Ryan W.; Freyberg, Zachary

doi:10.1101/2023.05.04.539488

Cited by 4 publications

(2 citation statements)

References 155 publications

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“…D1/D2-hybrid MSNs expressed conserved marker genes largely distinct from D1- and D2-MSNs (Figure 1E, S2S). These D1/D2-hybrid MSNs co-express both DRD1 and DRD2 transcripts at the single cell level (Figure S3), consistent with in situ mRNA hybridization and single cell RNA-seq data from both mouse 38, 39, 43 and non-human primates 37 . The average per cell type metrics showed more genes and unique transcripts in neurons (Number of genes Neurons = 7,318 ± 125; UMsI Neurons = 44,585 ± 1,301), compared to glial cells (Number of genes Neurons = 2,911 ± 74; UMsI Neurons = 8,433 ± 349; Figure S4).…”

Section: Resultssupporting

confidence: 83%

Single nuclei transcriptomics in human and non-human primate striatum implicates neuronal DNA damage and proinflammatory signaling in opioid use disorder

Phan

Ray

Xue

et al. 2023

Preprint

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The striatum in the brain is involved in various behavioral functions, including reward, and disease processes, such as opioid use disorder (OUD). Further understanding of the role of striatal subregions in reward behaviors and their potential associations with OUD requires molecular identification of specific striatal cell types in human brain. The human striatum contains subregions based on different anatomical, functional, and physiological properties, with the dorsal striatum further divided into caudate and putamen. Both caudate and putamen are associated with alterations in reward processing, formation of habits, and development of negative affect states in OUD. Using single nuclei RNA-sequencing of human postmortem caudate and putamen, we identified canonical neuronal cell types in striatum (e.g.,dopamine receptor 1 or 2 expressing neurons, D1 or D2) and less abundant subpopulations, including D1/D2 hybrid neurons and multiple classes of interneurons. By comparing unaffected subjects to subjects with OUD, we found neuronal-specific differences in pathways related to neurodegeneration, interferon response, and DNA damage. DNA damage markers were also elevated in striatal neurons of rhesus macaques following chronic opioid administration. We identified sex-dependent differences in the expression of stress-induced transcripts (e.g., FKBP5) among astrocytes and oligodendrocytes from female subjects with OUD. Thus, we describe striatal cell types and leverage these data to gain insights into molecular alterations in human striatum associated with opioid addiction.

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Section: Resultssupporting

confidence: 83%

Single nuclei transcriptomics in human and non-human primate striatum implicates neuronal DNA damage and proinflammatory signaling in opioid use disorder

Phan

Ray

Xue

et al. 2023

Preprint

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“…It enhances the responsiveness of dMSNs to glutamatergic inputs by binding to dopamine D1 receptors whereas it depresses the responsiveness of iMSNs by binding to D2 receptors ( Cepeda et al, 2001 ; Surmeier et al, 2010 ; Planert et al, 2013 ). Some striatal projection neurons co-express the two types of receptors and/or the D3 receptor but their function is unclear ( Gagnon et al, 2017 ; Gayden et al, 2023 also reviewed in Soghomonian, 2016 ). Current evidence indicates that the basal ganglia direct and indirect pathways are components of different cortico-striatal circuits, which may play distinct roles in ASD behavioral phenotypes.…”

Section: Cortical Control Of Striatal Neuronsmentioning

confidence: 99%

The cortico-striatal circuitry in autism-spectrum disorders: a balancing act

Soghomonian

2024

Front. Cell. Neurosci.

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The basal ganglia are major targets of cortical inputs and, in turn, modulate cortical function via their projections to the motor and prefrontal cortices. The role of the basal ganglia in motor control and reward is well documented and there is also extensive evidence that they play a key role in social and repetitive behaviors. The basal ganglia influence the activity of the cerebral cortex via two major projections from the striatum to the output nuclei, the globus pallidus internus and the substantia nigra, pars reticulata. This modulation involves a direct projection known as the direct pathway and an indirect projection via the globus pallidus externus and the subthalamic nucleus, known as the indirect pathway. This review discusses the respective contribution of the direct and indirect pathways to social and repetitive behaviors in neurotypical conditions and in autism spectrum disorders.

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Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder

Phan,

Ray,

Xue

et al. 2024

Nat Commun

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In brain, the striatum is a heterogenous region involved in reward and goal-directed behaviors. Striatal dysfunction is linked to psychiatric disorders, including opioid use disorder (OUD). Striatal subregions are divided based on neuroanatomy, each with unique roles in OUD. In OUD, the dorsal striatum is involved in altered reward processing, formation of habits, and development of negative affect during withdrawal. Using single nuclei RNA-sequencing, we identified both canonical (e.g., dopamine receptor subtype) and less abundant cell populations (e.g., interneurons) in human dorsal striatum. Pathways related to neurodegeneration, interferon response, and DNA damage were significantly enriched in striatal neurons of individuals with OUD. DNA damage markers were also elevated in striatal neurons of opioid-exposed rhesus macaques. Sex-specific molecular differences in glial cell subtypes associated with chronic stress were found in OUD, particularly female individuals. Together, we describe different cell types in human dorsal striatum and identify cell type-specific alterations in OUD.

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Integrative multi-dimensional characterization of striatal projection neuron heterogeneity in adult brain

Cited by 4 publications

References 155 publications

Single nuclei transcriptomics in human and non-human primate striatum implicates neuronal DNA damage and proinflammatory signaling in opioid use disorder

Single nuclei transcriptomics in human and non-human primate striatum implicates neuronal DNA damage and proinflammatory signaling in opioid use disorder

The cortico-striatal circuitry in autism-spectrum disorders: a balancing act

Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder

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