Cortical networks are composed of glutamatergic excitatory projection neurons and local GABAergic inhibitory interneurons that gate signal flow and sculpt network dynamics. Although they represent a ...minority of the total neocortical neuronal population, GABAergic interneurons are highly heterogeneous, forming functional classes based on their morphological, electrophysiological, and molecular features, as well as connectivity and in vivo patterns of activity. Here we review our current understanding of neocortical interneuron diversity and the properties that distinguish cell types. We then discuss how the involvement of multiple cell types, each with a specific set of cellular properties, plays a crucial role in diversifying and increasing the computational power of a relatively small number of simple circuit motifs forming cortical networks. We illustrate how recent advances in the field have shed light onto the mechanisms by which GABAergic inhibition contributes to network operations.
Tremblay et al. review our current knowledge of the diversity of neocortical GABAergic inhibitory interneurons and discuss how the intrinsic properties of interneuron subtypes contribute to specific computational properties within various circuit motifs formed between inhibitory and excitatory neurons.
Abstract
The objective of this study was to develop an accessible and accurate analysis method for microplastics that have been unintentionally added to cream cosmetic products. An experiment was ...performed on three cleansing creams in rich and viscous formulations. A spiked sample was prepared by adding polyethylene (PE) microspheres to the cleansing creams. After removing cosmetic ingredients from the creams using chemical digestion, damage to the PE microspheres was identified using Fourier transform infrared (FT-IR) spectroscopy. Field emission scanning electron microscopy (FE-SEM) images were obtained before and after digestion and used to characterize the morphology of the PE microspheres. The highest digestion efficiency was obtained using a chemical digestion method consisting of heating and stirring a sample in a 10 wt% KOH solution at 55 °C and 300 rpm for 5 days and did not damage the PE microspheres. The Nile red (9-diethylamino-5H-benzoαphenoxazine-5-one) staining method was effective in identifying small microplastics (< 106 μm). The optimal staining conditions are 5 μg/ml Nile red in
n
-hexane for green wavelengths.
Understanding translational control in gene expression relies on precise and comprehensive determination of translation initiation sites (TIS) across the entire transcriptome. The recently developed ...ribosome-profiling technique enables global translation analysis, providing a wealth of information about both the position and the density of ribosomes on mRNAs. Here we present an approach, global translation initiation sequencing, applying in parallel the ribosome E-site translation inhibitors lactimidomycin and cycloheximide to achieve simultaneous detection of both initiation and elongation events on a genome-wide scale. This approach provides a view of alternative translation initiation in mammalian cells with single-nucleotide resolution. Systemic analysis of TIS positions supports the ribosome linear-scanning mechanism in TIS selection. The alternative TIS positions and the associated ORFs identified by global translation initiation sequencing are conserved between human and mouse cells, implying physiological significance of alternative translation. Our study establishes a practical platform for uncovering the hidden coding potential of the transcriptome and offers a greater understanding of the complexity of translation initiation.
We present HiGlass, an open source visualization tool built on web technologies that provides a rich interface for rapid, multiplex, and multiscale navigation of 2D genomic maps alongside 1D genomic ...tracks, allowing users to combine various data types, synchronize multiple visualization modalities, and share fully customizable views with others. We demonstrate its utility in exploring different experimental conditions, comparing the results of analyses, and creating interactive snapshots to share with collaborators and the broader public. HiGlass is accessible online at http://higlass.io and is also available as a containerized application that can be run on any platform.
Concepts of solid-state NMR spectroscopy and applications to fluid membranes are reviewed in this paper. Membrane lipids with 2H-labeled acyl chains or polar head groups are studied using 2H NMR to ...yield knowledge of their atomistic structures in relation to equilibrium properties. This review demonstrates the principles and applications of solid-state NMR by unifying dipolar and quadrupolar interactions and highlights the unique features offered by solid-state 2H NMR with experimental illustrations. For randomly oriented multilamellar lipids or aligned membranes, solid-state 2H NMR enables direct measurement of residual quadrupolar couplings (RQCs) due to individual C–2H-labeled segments. The distribution of RQC values gives nearly complete profiles of the segmental order parameters S CD (i) as a function of acyl segment position (i). Alternatively, one can measure residual dipolar couplings (RDCs) for natural abundance lipid samples to obtain segmental S CH order parameters. A theoretical mean-torque model provides acyl-packing profiles representing the cumulative chain extension along the normal to the aqueous interface. Equilibrium structural properties of fluid bilayers and various thermodynamic quantities can then be calculated, which describe the interactions with cholesterol, detergents, peptides, and integral membrane proteins and formation of lipid rafts. One can also obtain direct information for membrane-bound peptides or proteins by measuring RDCs using magic-angle spinning (MAS) in combination with dipolar recoupling methods. Solid-state NMR methods have been extensively applied to characterize model membranes and membrane-bound peptides and proteins, giving unique information on their conformations, orientations, and interactions in the natural liquid-crystalline state.
Higher-order sensory thalamic nuclei are densely connected with multiple cortical and subcortical areas, yet the role of these nuclei remains elusive. The posteromedial thalamic nucleus (POm), the ...higher-order thalamic nucleus in the rodent somatosensory system, is an anatomical hub broadly connected with multiple sensory and motor brain areas yet weakly responds to passive sensory stimulation and whisker movements. To understand the role of POm in sensory perception, we developed a self-initiated, two-alternative forced-choice task in freely moving mice during active sensing. Using optogenetic and chemogenetic manipulation, we show that POm plays a significant role in sensory perception and the projection from the primary somatosensory cortex to POm is critical for the contribution of POm in sensory perception during active sensing.
A highly diverse population of neocortical GABAergic inhibitory interneurons has been implicated in multiple functions in information processing within cortical circuits. The diversity of cortical ...interneurons is determined during development and primarily depends on their embryonic origins either from the medial (MGE) or the caudal (CGE) ganglionic eminences. Although MGE-derived parvalbumin (PV)- or somatostatin (SST)-expressing interneurons are well characterized, less is known about the other types of cortical GABAergic interneurons, especially those of CGE lineage, because of the lack of specific neuronal markers for these interneuron subtypes. Using a bacterial artificial chromosome transgenic mouse line, we show that, in the somatosensory cortex of the mouse, the serotonin 5-hydroxytryptamine 3A (5-HT(3A)) receptor, the only ionotropic serotonergic receptor, is expressed in most, if not all, neocortical GABAergic interneurons that do not express PV or SST. Genetic fate mapping and neurochemical profile demonstrate that 5-HT(3A)R-expressing neurons include the entire spectrum of CGE-derived interneurons. We report that, in addition to serotonergic responsiveness via 5-HT(3A)Rs, acetylcholine also depolarizes 5-HT(3A)R-expressing neurons via nicotinic receptors. 5-HT(3A)R-expressing neurons in thalamocortical (TC) recipient areas receive weak but direct monosynaptic inputs from the thalamus. TC input depolarizes a subset of TC-recipient 5-HT(3A)R neurons as strongly as fast-spiking cells, in part because of their high input resistance. Hence, fast modulation of serotonergic and cholinergic transmission may influence cortical activity through an enhancement of GABAergic synaptic transmission from 5-HT(3A)R-expressing neurons during sensory process depending on different behavioral states.
Neurons live for decades in a postmitotic state, their genomes susceptible to DNA damage. Here we survey the landscape of somatic single-nucleotide variants (SNVs) in the human brain. We identified ...thousands of somatic SNVs by single-cell sequencing of 36 neurons from the cerebral cortex of three normal individuals. Unlike germline and cancer SNVs, which are often caused by errors in DNA replication, neuronal mutations appear to reflect damage during active transcription. Somatic mutations create nested lineage trees, allowing them to be dated relative to developmental landmarks and revealing a polyclonal architecture of the human cerebral cortex. Thus, somatic mutations in the brain represent a durable and ongoing record of neuronal life history, from development through postmitotic function.
Data analysis often entails a multitude of heterogeneous steps, from the application of various command line tools to the usage of scripting languages like R or Python for the generation of plots and ...tables. It is widely recognized that data analyses should ideally be conducted in a reproducible way. Reproducibility enables technical validation and regeneration of results on the original or even new data. However, reproducibility alone is by no means sufficient to deliver an analysis that is of lasting impact (i.e., sustainable) for the field, or even just one research group. We postulate that it is equally important to ensure adaptability and transparency. The former describes the ability to modify the analysis to answer extended or slightly different research questions. The latter describes the ability to understand the analysis in order to judge whether it is not only technically, but methodologically valid.
Here, we analyze the properties needed for a data analysis to become reproducible, adaptable, and transparent. We show how the popular workflow management system Snakemake can be used to guarantee this, and how it enables an ergonomic, combined, unified representation of all steps involved in data analysis, ranging from raw data processing, to quality control and fine-grained, interactive exploration and plotting of final results.
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