Microglia play a key role in shaping the formation and refinement of the excitatory network of the brain. However, less is known about whether and how they organize the development of distinct inhibitory networks. We find that microglia are essential for the proper development of somatostatin-positive (SST) cell synapses during the second postnatal week. We further identify a pair of molecules that act antagonistically to one another in the organization of SST cell axonal elaboration. Whereas CX3CL1 acts to suppress axonal growth and complexity, CXCL12 promotes it. Assessing the functional importance of microglia in the development of cortical activity, we find that a whisker stimulation paradigm that drives SST cell activation leads to reduced cortical spiking in brains depleted of microglia. Collectively, our data demonstrate an important role of microglia in regulating the development of SST cell output early in life.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396528 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2022.111209 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Update on regulation of GHRH and its actions on GH secretion in health and disease.
Rev Endocr Metab Disord
January 2025
Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, Chicago, IL, USA.
This review focuses on our current understanding of how growth hormone releasing hormone (GHRH): 1) stimulates GH release and synthesis from pituitary growth hormone (GH)-producing cells (somatotropes), 2) drives somatotrope proliferation, 3) is negatively regulated by somatostatin (SST), GH and IGF1, 4) is altered throughout lifespan and in response to metabolic challenges, and 5) analogues can be used clinically to treat conditions of GH excess or deficiency. Although a large body of early work provides an underpinning for our current understanding of GHRH, this review specifically highlights more recent work that was made possible by state-of-the-art analytical tools, receptor-specific agonists and antagonists, high-resolution in vivo and ex vivo imaging and the development of tissue (cell) -specific ablation mouse models, to paint a more detailed picture of the regulation and actions of GHRH.
View Article and Find Full Text PDFMixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus.
Elife
January 2025
Department of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, United States.
The basal ganglia (BG) are an evolutionarily conserved and phylogenetically old set of sub-cortical nuclei that guide action selection, evaluation, and reinforcement. The entopeduncular nucleus (EP) is a major BG output nucleus that contains a population of GABA/glutamate cotransmitting neurons (EP) that specifically target the lateral habenula (LHb) and whose function in behavior remains mysterious. Here, we use a probabilistic switching task that requires an animal to maintain flexible relationships between action selection and evaluation to examine when and how GABA/glutamate cotransmitting neurons contribute to behavior.
View Article and Find Full Text PDFhomeRNA self-blood collection enables high-frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection: a prospective cohort study.
EBioMedicine
January 2025
Department of Chemistry, University of Washington, Seattle, WA, USA; Department of Urology, University of Washington, Seattle, WA, USA. Electronic address:
Background: Early host immunity to acute respiratory infections (ARIs) is heterogenous, dynamic, and critical to an individual's infection outcome. Due to limitations in sampling frequency/timepoints, kinetics of early immune dynamics in natural human infections remain poorly understood. In this nationwide prospective cohort study, we leveraged a Tasso-SST based self-blood collection and stabilization tool (homeRNA) to profile detailed kinetics of the presymptomatic to convalescence host immunity to contemporaneous respiratory pathogens.
View Article and Find Full Text PDFNeocortical somatostatin neuron diversity in cognition and learning.
Trends Neurosci
January 2025
Department of Biological Sciences and Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA, USA. Electronic address:
Somatostatin-expressing (SST) neurons are a major class of electrophysiologically and morphologically distinct inhibitory cells in the mammalian neocortex. Transcriptomic data suggest that this class can be divided into multiple subtypes that are correlated with morpho-electric properties. At the same time, availability of transgenic tools to identify and record from SST neurons in awake, behaving mice has stimulated insights about their response properties and computational function.
View Article and Find Full Text PDFEnabling next-generation engineered TCR-T therapies based on high-throughput TCR discovery from diagnostic tumor biopsies.
Nat Commun
January 2025
Neogene Therapeutics, A member of the AstraZeneca Group, Amsterdam, The Netherlands.
Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate tumor regression, including complete and durable responses, in a range of solid cancers, most notably in melanoma. However, its wider application and efficacy has been restricted by the limited accessibility, proliferative capacity and effector function of tumor-specific TIL. Here, we develop a platform for the efficient identification of tumor-specific TCR genes from diagnostic tumor biopsies, including core-needle biopsies frozen in a non-viable format, to enable engineered T cell therapy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!