The mammalian neocortex gives rise to a wide range of mental activities and consists of a constellation of interconnected areas that are built from a set of basic circuit templates. Major obstacles ...to understanding cortical architecture include the diversity of cell types, their highly recurrent local and global connectivity, dynamic circuit operations, and a convoluted developmental assembly process rooted in the genome. With our increasing knowledge of gene expression and developmental genetic principles, it is now feasible to launch a program of genetic dissection of cortical circuits through systematic targeting of cell types and fate mapping of neural progenitors. Strategic design of even a modest number of mouse driver lines will facilitate efforts to compile a cell type parts list, build a Cortical Cell Atlas, establish experimental access to modern tools, integrate studies across levels, and provide coordinates for tracing developmental trajectory from circuit assembly to functional operation.
In this article, Huang argues that it is necessary and feasible to launch a program of genetic dissection of neural circuits of the cerebral cortex in the mouse through systematic targeting and fate mapping of cell types.
In this paper, we propose a novel surface subdivision scheme called non‐box subdivision, which is generalized from four‐directional S13 non‐box splines. The resulting subdivision surfaces achieve C1 ...continuity with the convex hull property. This scheme can be regarded as either a four‐directional subdivision or a special quadrilateral subdivision. When used as a quadrilateral subdivision, the proposed scheme can control the shape of the limit surface more flexibly than traditional schemes due to the natural introduction of auxiliary face control vertices.
The phenotypic diversity of cortical GABAergic neurons is probably necessary for their functional versatility in shaping the spatiotemporal dynamics of neural circuit operations underlying cognition. ...Deciphering the logic of this diversity requires comprehensive analysis of multi-modal cell features and a framework of neuronal identity that reflects biological mechanisms and principles. Recent high-throughput single-cell analyses have generated unprecedented data sets characterizing the transcriptomes, morphology and electrophysiology of interneurons. We posit that cardinal interneuron types can be defined by their synaptic communication properties, which are encoded in key transcriptional signatures. This conceptual framework integrates multi-modal cell features, captures neuronal input-output properties fundamental to circuit operation and may advance understanding of the appropriate granularity of neuron types, towards a biologically grounded and operationally useful interneuron taxonomy.
To understand the organization and assembly of mammalian brain circuits, we need a comprehensive tool set that can address the challenges of cellular diversity, spatial complexity at synapse ...resolution, dynamic complexity of circuit operations, and multifaceted developmental processes rooted in the genome. Complementary to physics- and chemistry-based methods, genetic tools tap into intrinsic cellular and developmental mechanisms. Thus, they have the potential to achieve appropriate spatiotemporal resolution and the cellular-molecular specificity necessary for observing and probing the makings and inner workings of neurons and neuronal circuits. Furthermore, genetic analysis will be key to unraveling the intricate link from genes to circuits to systems, in part through systematic targeting and tracking of individual cellular components of neural circuits. Here we review recent progress in genetic tool development and advances in genetic analysis of neural circuits in the mouse. We also discuss future directions and implications for understanding brain disorders.
Interest in why firms conduct environmental, social and governance (ESG) activity is longstanding and increasing. Our understanding, however, remains fragmented with alternative accounts that seek to ...explain the relationship between ESG performance (ESGP) and corporate financial performance (CFP). This paper reviews alternative accounts for the relationship and finds that the weight of empirical evidence shows a positive, statistically significant but economically modest ESGP–CFP link, consistent with theoretical expectations. This economically modest relationship suggests ESG activity is unlikely to be primarily motivated by narrow measures of CFP. Further scholarship viewing ESG as part of overall firm activity would be constructive.
A key obstacle to understanding neural circuits in the cerebral cortex is that of unraveling the diversity of GABAergic interneurons. This diversity poses general questions for neural circuit ...analysis: how are these interneuron cell types generated and assembled into stereotyped local circuits and how do they differentially contribute to circuit operations that underlie cortical functions ranging from perception to cognition? Using genetic engineering in mice, we have generated and characterized approximately 20 Cre and inducible CreER knockin driver lines that reliably target major classes and lineages of GABAergic neurons. More select populations are captured by intersection of Cre and Flp drivers. Genetic targeting allows reliable identification, monitoring, and manipulation of cortical GABAergic neurons, thereby enabling a systematic and comprehensive analysis from cell fate specification, migration, and connectivity, to their functions in network dynamics and behavior. As such, this approach will accelerate the study of GABAergic circuits throughout the mammalian brain.
► Generation of ∼20 Cre lines targeting major classes of cortical interneurons ► Intersection of Cre and Flp lines increases specificity of targeting ► Genetic targeting enables systematic and comprehensive analysis of cortical interneurons ► Genetic targeting accelerates the study of GABAergic circuits throughout the mammalian brain
The basolateral amygdala (BLA) plays essential roles in behaviors motivated by stimuli with either positive or negative valence, but how it processes motivationally opposing information and ...participates in establishing valence-specific behaviors remains unclear. Here, by targeting Fezf2-expressing neurons in the BLA, we identify and characterize two functionally distinct classes in behaving mice, the negative-valence neurons and positive-valence neurons, which innately represent aversive and rewarding stimuli, respectively, and through learning acquire predictive responses that are essential for punishment avoidance or reward seeking. Notably, these two classes of neurons receive inputs from separate sets of sensory and limbic areas, and convey punishment and reward information through projections to the nucleus accumbens and olfactory tubercle, respectively, to drive negative and positive reinforcement. Thus, valence-specific BLA neurons are wired with distinctive input-output structures, forming a circuit framework that supports the roles of the BLA in encoding, learning and executing valence-specific motivated behaviors.
Single-cell RNA-sequencing (scRNA-seq) technology provides a new avenue to discover and characterize cell types; however, the experiment-specific technical biases and analytic variability inherent to ...current pipelines may undermine its replicability. Meta-analysis is further hampered by the use of ad hoc naming conventions. Here we demonstrate our replication framework, MetaNeighbor, that quantifies the degree to which cell types replicate across datasets, and enables rapid identification of clusters with high similarity. We first measure the replicability of neuronal identity, comparing results across eight technically and biologically diverse datasets to define best practices for more complex assessments. We then apply this to novel interneuron subtypes, finding that 24/45 subtypes have evidence of replication, which enables the identification of robust candidate marker genes. Across tasks we find that large sets of variably expressed genes can identify replicable cell types with high accuracy, suggesting a general route forward for large-scale evaluation of scRNA-seq data.
The response of cortical neurons to a sensory stimulus is modulated by the context. In the visual cortex, for example, stimulation of a pyramidal cell's receptive-field surround can attenuate the ...cell's response to a stimulus in the centre of its receptive field, a phenomenon called surround suppression. Whether cortical circuits contribute to surround suppression or whether the phenomenon is entirely relayed from earlier stages of visual processing is debated. Here we show that, in contrast to pyramidal cells, the response of somatostatin-expressing inhibitory neurons (SOMs) in the superficial layers of the mouse visual cortex increases with stimulation of the receptive-field surround. This difference results from the preferential excitation of SOMs by horizontal cortical axons. By perturbing the activity of SOMs, we show that these neurons contribute to pyramidal cells' surround suppression. These results establish a cortical circuit for surround suppression and attribute a particular function to a genetically defined type of inhibitory neuron.
Quantum data are susceptible to decoherence induced by the environment and to errors in the hardware processing it. A future fault-tolerant quantum computer will use quantum error correction to ...actively protect against both. In the smallest error correction codes, the information in one logical qubit is encoded in a two-dimensional subspace of a larger Hilbert space of multiple physical qubits. For each code, a set of non-demolition multi-qubit measurements, termed stabilizers, can discretize and signal physical qubit errors without collapsing the encoded information. Here using a five-qubit superconducting processor, we realize the two parity measurements comprising the stabilizers of the three-qubit repetition code protecting one logical qubit from physical bit-flip errors. While increased physical qubit coherence times and shorter quantum error correction blocks are required to actively safeguard the quantum information, this demonstration is a critical step towards larger codes based on multiple parity measurements.
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