1,721,022 research outputs found
The Neuron Identity Problem: Form Meets Function
A complete understanding of nervous system function cannot be achieved without the identification of its component cell types. In this Perspective, we explore a series of related issues surrounding cell identity and how revolutionary methods for labeling and probing specific neuronal types have clarified this question. Specifically, we ask the following questions: what is the purpose of such diversity, how is it generated, how is it maintained, and, ultimately, how can one unambiguously identity one cell type from another? We suggest that each cell type can be defined by a unique and conserved molecular ground state that determines its capabilities. We believe that gaining an understanding of these molecular barcodes will advance our ability to explore brain function, enhance our understanding of the biochemical basis of CNS disorders, and aid in the development of novel therapeutic strategies
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Multimodal classification of neurons in the lateral septum
The lateral septum (LS) is a nucleus in the ventral forebrain that modulates complex social and affective behaviors. However, the specific mechanisms through which LS neurons influence these behaviors remain unclear, as the existing research has often yielded ambiguous or conflicting findings. This ambiguity can largely be attributed to a lack of cell-type specificity. While functionally and anatomically distinct LS neurons have been identified, a comprehensive multimodal classification of neurons in the LS is currently lacking. To address this, we profiled the transcriptional identity of mature LS neurons originating from either the rostral or caudal embryonic septum. Our findings revealed 12 transcriptionally distinct subtypes of LS neurons that fall into two main groups: those that have a history of Nkx2.1 expression (Nkx2.1-neurons) and those that do not. Interestingly, we found that developmentally distinct subtypes can be transcriptionally related, and that Nkx2.1-neurons displayed a differential enrichment for cell adhesion and communication molecules compared to other LS neurons. We then examined the spatial relationships of neurons in the LS and discovered each subtype occupies a discrete anatomical domain. Notably, these domains are overlayed by patterns of gene expression that correlated with the transcriptional taxonomy of LS neuron subtypes. Lastly, we leveraged our transcriptomic data to label non-overlapping subgroups of LS neurons, and detail their connective, morphological, and electrophysiological properties. Our findings offer a deeper understanding of neuronal heterogeneity in the LS, paving the way for targeted studies to discern how the defining characteristics of these cells influence the behaviors they modulate
Dynamic FoxG1 Expression Coordinates the Integration of Multipolar Pyramidal Neuron Precursors into the Cortical Plate
SummaryPyramidal cells of the cerebral cortex are born in the ventricular zone and migrate through the intermediate zone to enter into the cortical plate. In the intermediate zone, these migrating precursors move tangentially and initiate the extension of their axons by transiently adopting a characteristic multipolar morphology. We observe that expression of the forkhead transcription factor FoxG1 is dynamically regulated during this transitional period. By utilizing conditional genetic strategies, we show that the downregulation of FoxG1 at the beginning of the multipolar cell phase induces Unc5D expression, the timing of which ultimately determines the laminar identity of pyramidal neurons. In addition, we demonstrate that the re-expression of FoxG1 is required for cells to transit out of the multipolar cell phase and to enter into the cortical plate. Thus, the dynamic expression of FoxG1 during migration within the intermediate zone is essential for the proper assembly of the cerebral cortex
Pyramidal Neurons Grow Up and Change Their Mind
The precise stereotypic projections of pyramidal neurons within the six-layered cortex of mammals are key in allowing this structure to attain its high level of function. Recent studies have provided the first indications that postmitotic transcription factors are required for the formation and maintenance of both corticofugal and intracortical pyramidal cell populations. Here, we discuss these new findings in the context of our present understanding of cortical cell specification
Cortex Shatters the Glass Ceiling
Recreating developmental structures in vitro has been a primary challenge for stem cell biologists. Recent studies in Cell Stem Cell (Eiraku et al., 2008) and Nature (Gaspard et al., 2008) demonstrate that embryonic stem cells can recapitulate early cortical development, enabling them to generate specific cortical subtypes
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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