Single-Cell Analysis of Foxp1-Driven Mechanisms Essential for Striatal Development DOI Creative Commons
Ashley G. Anderson, Ashwinikumar Kulkarni, Matthew J. Harper

et al.

Cell Reports, Journal Year: 2020, Volume and Issue: 30(9), P. 3051 - 3066.e7

Published: March 1, 2020

The striatum is a critical forebrain structure integrating cognitive, sensory, and motor information from diverse brain regions into meaningful behavioral output. However, the transcriptional mechanisms underlying striatal development at single-cell resolution remain unknown. Using RNA sequencing (RNA-seq), we examine cellular diversity of early postnatal show that Foxp1, transcription factor strongly linked to autism intellectual disability, regulates composition, neurochemical architecture, connectivity in cell-type-dependent fashion. We also identify Foxp1-regulated target genes within distinct cell types connect these molecular changes functional deficits relevant phenotypes described patients with FOXP1 loss-of-function mutations. this approach, could non-cell-autonomous effects produced by disrupting one type compensation occurs other populations. These data reveal cell-type-specific regulated Foxp1 underlie features circuitry.

Language: Английский

Super-resolution microscopy demystified DOI
Lothar Schermelleh, Alexia Ferrand, Thomas Huser

et al.

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 21(1), P. 72 - 84

Published: Dec. 17, 2018

Language: Английский

Citations

1004
Expansion microscopy: principles and uses in biological research DOI

Asmamaw T. Wassie,

Yongxin Zhao,

Edward S. Boyden

et al.

Nature Methods, Journal Year: 2018, Volume and Issue: 16(1), P. 33 - 41

Published: Dec. 6, 2018

Language: Английский

Citations

421
PINK1 and Parkin: emerging themes in mitochondrial homeostasis DOI Creative Commons
Thomas G. McWilliams, Miratul M. K. Muqit

Current Opinion in Cell Biology, Journal Year: 2017, Volume and Issue: 45, P. 83 - 91

Published: April 1, 2017

The Parkinson's disease (PD)-associated protein kinase, PTEN-induced putative kinase1 (PINK1), and ubiquitin E3 ligase Parkin, function in a common signalling pathway known to regulate mitochondrial network homeostasis quality control, including mitophagy. multistep activation of this pathway, as well an unexpected convergence between the post-translational modifications ubiquitylation phosphorylation, has added breadth our understanding cellular damage responses during human disease. In concert with these new insights signal transduction, unique modalities signatures vertebrate mitophagy have been unravelled vivo for very first time. cell biology mammalian mitophagy, roles PINK1-Parkin emerged be more complex than previously thought.

Language: Английский

Citations

286
Monitoring and Updating of Action Selection for Goal-Directed Behavior through the Striatal Direct and Indirect Pathways DOI Creative Commons
Satoshi Nonomura, Kayo Nishizawa, Yutaka Sakai

et al.

Neuron, Journal Year: 2018, Volume and Issue: 99(6), P. 1302 - 1314.e5

Published: Aug. 23, 2018

Language: Английский

Citations

182
The Striosome and Matrix Compartments of the Striatum: A Path through the Labyrinth from Neurochemistry toward Function DOI Creative Commons
Katherine R. Brimblecombe, Stephanie J. Cragg

ACS Chemical Neuroscience, Journal Year: 2016, Volume and Issue: 8(2), P. 235 - 242

Published: Dec. 1, 2016

The striatum is a heterogeneous structure with diverse range of neuron types and neuromodulators. Three decades anatomical biochemical studies have established that the neurochemical organization not uniformly heterogeneous, but rather, can be differentiated into neurochemically discrete compartments known as striosomes (also patches) matrix. These are well understood to differ in their expression markers, some differences afferent efferent connectivity also been suggested different involvement neurological diseases. However, functional outcomes striosome-matrix poorly understood. Now, recent findings new experimental tools beginning reveal distinctions between matrix distinct consequences for striatal synapse function. Here, we review suggest there regulation neural function striosome versus compartments, particularly compartment-specific interactions. We highlight transgenic viral becoming available should now accelerate pace advances understanding these long-mysterious compartments.

Language: Английский

Citations

169
Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice DOI Creative Commons
In Bum Lee, Eugene Lee,

Nicholas A Han

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 8, 2024

Abstract Compulsive behaviors are observed in a range of psychiatric disorders, however the neural substrates underlying not clearly defined. Here we show that basolateral amygdala-dorsomedial striatum (BLA-DMS) circuit activation leads to manifestation compulsive-like behaviors. We revealed BLA neurons projecting DMS, mainly onto dopamine D1 receptor-expressing neurons, largely overlap with neuronal population responds aversive predator stress, widely used anxiogenic stressor. Specific optogenetic BLA-DMS induced strong anxiety response followed by compulsive grooming. Furthermore, developed mouse model for compulsivity displaying wide spectrum chronically activating circuit. In these mice, persistent molecular changes at synapses were causally related phenotypes. Together, our study demonstrates involvement emergence enduring via its synaptic changes.

Language: Английский

Citations

19
Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder DOI Creative Commons
BaDoi N. Phan, Madelyn H. Ray, Xiangning Xue

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 31, 2024

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

Language: Английский

Citations

18
The striatal matrix compartment is expanded in autism spectrum disorder DOI Creative Commons
Jeff L. Waugh, Ayman Hassan,

Adrian T. Funk

et al.

Journal of Neurodevelopmental Disorders, Journal Year: 2025, Volume and Issue: 17(1)

Published: Feb. 15, 2025

Abstract Background Autism spectrum disorder (ASD) is the second-most common neurodevelopmental in childhood. This complex developmental manifests with restricted interests, repetitive behaviors, and difficulties communication social awareness. The inherited acquired causes of ASD impact many diverse brain regions, challenging efforts to identify a shared neuroanatomical substrate for this range symptoms. striatum its connections are among most implicated sites abnormal structure and/or function ASD. Striatal projection neurons develop segregated tissue compartments, matrix striosome, that histochemically, pharmacologically, functionally distinct. Immunohistochemical assessment animal models autism described matrix:striosome volume ratios, an possible shift from striosome volume. Shifting ratio could result expansion matrix, reduction spatial redistribution or combination these changes. Each type ratio-shifting abnormality may predispose but yield different combinations features. Methods We developed cohort 426 children adults (213 matched ASD-control pairs) performed connectivity-based parcellation (diffusion tractography) striatum. identified voxels matrix-like striosome-like patterns structural connectivity. Results Matrix-like was increased ASD, no evident change organization compartment. inter-compartment difference (matrix minus striosome) within each individual 31% larger both caudate putamen, somatotopic zones throughout rostral-caudal extent Subjects moderate elevations ADOS (Autism Diagnostic Observation Schedule) scores had volume, those highly elevated 3.7-fold increases Conclusions Matrix embedded distinct functional networks, suggesting compartment-selective injury maldevelopment mediate specific clinical Previously, assessing striatal compartments humans required post mortem tissue. provides means assess neuropsychiatric diseases compartment-specific abnormalities. While other mechanisms also increase chance developing social, sensory, motor phenotypes

Language: Английский

Citations

2
Chronic Stress Alters Striosome-Circuit Dynamics, Leading to Aberrant Decision-Making DOI Creative Commons

Alexander Friedman,

Daigo Homma,

Bernard Bloem

et al.

Cell, Journal Year: 2017, Volume and Issue: 171(5), P. 1191 - 1205.e28

Published: Nov. 1, 2017

Language: Английский

Citations

144
Emerging Trends in Micro- and Nanoscale Technologies in Medicine: From Basic Discoveries to Translation DOI Creative Commons
Mario Moisés Álvarez, Joanna Aizenberg,

Mostafa Analoui

et al.

ACS Nano, Journal Year: 2017, Volume and Issue: 11(6), P. 5195 - 5214

Published: May 19, 2017

We discuss the state of art and innovative micro- nanoscale technologies that are finding niches opening up new opportunities in medicine, particularly diagnostic therapeutic applications. take design point-of-care applications capture circulating tumor cells as illustrative examples integration nanotechnologies into solutions challenges. describe several novel enable imaging cellular structures molecular events. In therapeutics, we utilization including drug delivery, tissue engineering, pharmaceutical development/testing. addition, relevant challenges face achieving cost-effective widespread clinical implementation well forecasted medicine.

Language: Английский

Citations

120