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So, N.

Publications and source records attributed to So, N..

5 recordsLinked to original sources

Behavioral demands organize a decision process into distinct yet coordinated neural representations in parietal cortex

Perceptual decisions are widely modeled as the accumulation of evidence to a bound. In the lateral intraparietal area (LIP), this computation is thought to be implemented in a low-dimensional population representation organized around the single action used to report the choice, consistent with an intentional framework. The intentional framework, however, implies that changing the behavioral demands on the report should change the representation itself, raising a question about the generality of the low-dimensional decision representation described in LIP: is it a special case of decisions reported through a single action, or does it reflect a more general computational architecture that can support multiple behavioral outputs? We tested this by training monkeys to report the \textit{termination} of a motion-discrimination decision with a saccade to a choice-neutral target, and its \textit{content} only later, with a saccade to one of two choice targets. Even though the two reports were behaviorally separable, the timing of termination remained systematically linked to the accumulation of sensory evidence supporting the eventual choice in both monkeys, indicating that both reports continued to draw on a common underlying computation. Using high-density Neuropixels recordings from LIP, however, we found that decision termination and decision content were represented along orthogonal population coding directions supported by largely non-overlapping groups of neurons. Yet the two representations were not independent: trial-by-trial fluctuations in the population encoding content predicted subsequent fluctuations in the population encoding termination, with their coupling strengthening as the decision evolved. These results suggest that a single decision computation can be flexibly reformatted into distinct, action-specific representations, coordinated by selective transfer of information between neural populations.

neuroscience↗

Transfer of graded information through gated receptivity to widely broadcast signals

Making accurate decisions requires the brain to maintain evolving representations of the evidence supporting different possible choices. The population of neurons that maintains this evolving representation may change over the course of the decision-making process. Such changes may result from a switch in the set of neurons representing the relevant behavioral output or a switch in the set of neurons receiving task-relevant information. Recent work has shown how intervening actions like eye movements or navigation to a new location can shift the set of neurons that encode subsequent inputs and outputs. Here, we present a computational model of how analog-valued information that supports an evolving decision can be flexibly transferred between populations of neurons without changing the synaptic connectivity of the underlying network. This is accomplished through a dynamic gating mechanism in which information is widely broadcast throughout a network, but only those neurons receiving a gating signal are receptive to this information. Using this framework, we provide a mechanistic explanation for recent experimental results in which information supporting an evolving decision was shown to be transferred between different populations of parietal cortex neurons during intervening smooth pursuit and saccadic eye movements. This mechanism enables organisms to maintain a continuous decision process despite changing frames of reference, offering a potentially general framework for cognitive continuity in dynamic environments.

neuroscience↗

Functional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning

The fusion peptide of SARS-CoV-2 spike protein is functionally important for membrane fusion during virus entry and is part of a broadly neutralizing epitope. However, sequence determinants at the fusion peptide and its adjacent regions for pathogenicity and antigenicity remain elusive. In this study, we performed a series of deep mutational scanning (DMS) experiments on an S2 region spanning the fusion peptide of authentic SARS-CoV-2 in different cell lines and in the presence of broadly neutralizing antibodies. We identified mutations at residue 813 of the spike protein that reduced TMPRSS2-mediated entry with decreased virulence. In addition, we showed that an F823Y mutation, present in bat betacoronavirus HKU9 spike protein, confers resistance to broadly neutralizing antibodies. Our findings provide mechanistic insights into SARS-CoV-2 pathogenicity and also highlight a potential challenge in developing broadly protective S2-based coronavirus vaccines.

microbiology↗

Widespread impact of immunoglobulin V gene allelic polymorphisms on antibody reactivity

The ability of human immune system to generate antibodies to any given antigen can be strongly influenced by immunoglobulin V gene (IGV) allelic polymorphisms. However, previous studies have provided only a limited number of examples. Therefore, the prevalence of this phenomenon has been unclear. By analyzing >1,000 publicly available antibody-antigen structures, we show that many IGV allelic polymorphisms in antibody paratopes are determinants for antibody binding activity. Biolayer interferometry experiment further demonstrates that paratope allelic mutations on both heavy and light chain often abolish antibody binding. We also illustrate the importance of minor IGV allelic variants with low frequency in several broadly neutralizing antibodies to SARS-CoV-2 and influenza virus. Overall, this study not only highlights the pervasive impact of IGV allelic polymorphisms on antibody binding, but also provides mechanistic insights into the variability of antibody repertoires across individuals, which in turn have important implications for vaccine development and antibody discovery.

immunology↗

Decision formation in parietal cortex transcends a fixed frame of reference

Neurons in the lateral intraparietal cortex (area LIP) represent the formation of a decision when it is linked to a specific action, such as an eye movement to a choice target. However, these neurons should be unable to represent a decision that transpires across actions that would disrupt this linkage. We investigated this limitation by recording simultaneously from many neurons. While intervening actions disrupt the representation by single neurons, the ensemble achieves continuity of the decision process by passing information from currently active neurons to neurons that will become active after the action. In this way, the representation of an evolving decision can be generalized across actions and transcends the frame of reference that specifies the neural response fields. The finding extends previous observations of receptive field remapping, thought to support the stability of perception across eye movements, to the continuity of a thought process, such as a decision.

neuroscience↗