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Corbo, J.

Publications and source records attributed to Corbo, J..

6 recordsLinked to original sources

Geometric reshaping of task-relevant representations in the primary visual cortex supports perceptual decisions

Discriminating between two stimuli requires that their neural representations become separable by downstream readouts. This can be achieved geometrically, by disentangling the manifolds that population responses form in neural state space. Such reorganization has been observed in associative and motor areas, but never at the earliest stage of cortical processing. While task learning is known to impact neuronal representations in the primary visual cortex (V1), it is unknown if the population geometry is also reshaped to support perceptual decisions. We imaged V1 populations in mice trained on a Go/NoGo orientation discrimination task of increasing difficulty, and in naive mice passively viewing the same stimuli. Training reshaped the representational geometry so that the population responses were better linearly separable. A static compression made the Go and NoGo manifolds more compact and lower-dimensional from the earliest response, while a dynamic separation drove them further apart through the trial. Together, those transformations increased manifold capacity and readout accuracy. This reorganization made the Go-NoGo relationship in the neural state space more stable in Trained animals than in Naive ones. Within this learned geometry, the position of individual trials along the Go-NoGo axis predicted the animals' decision probabilities. Learning therefore promotes a disentangled and stable representational geometry that feeds the decision process.

neuroscience↗

Modulation of Avian Iridescence via Malanogenesis

The iridescent colors of birds originate in nanoscale feather structures that interact with light. Although the physical principles governing avian iridescence are well-established, the molecular mechanisms assembling these nanostructures into photonic materials remain unknown. Here, we integrated genomic, cellular, and optical approaches to investigate the molecular basis of iridescent color formation in birds. We leveraged mutations that arose in the domesticated Indian peafowl and natural color variation in wild birds. In peafowl, we identified eight genes underlying gains, losses, and shifts of iridescence, whereas in two wild species, we used single-cell transcriptomics to profile asymmetric feathers in which iridescent and non-iridescent barbules develop on opposite sides of the same feather. We found that all peafowl mutations mapped to melanogenesis genes, showing that variation in this pathway can modify diverse geometric features of feather photonic nanostructures. Mutations altering melanin composition collapsed multilayered photonic systems and yielded non-iridescent tissues, whereas changes in melanosome abundance, elongation, or deposition timing generated multilayer architectures with variable periodicity and color. We further show in peafowl that transitions from non-iridescent to iridescent plumage were associated with single-nucleotide mutations in a melanogenesis gene, suggesting that, in species already capable of forming multilayered nanostructures, iridescence can be gained by relatively small genetic changes. Single-cell transcriptomes from wild species also supported extensive melanocyte-centered regulatory rewiring associated with iridescence, including changes in melanosome maturation, trafficking, and intercellular signaling. Together, these results show that the nanoscale order underlying iridescence is developmentally plastic and highly responsive to the melanogenic environment. Significance StatementBird feathers can produce brilliant, shifting colors, but how these colors form during development has remained poorly understood. By comparing the genomes of color variants of domesticated peafowl and transcriptomes during feather development in wild birds, and combining these with chemical and optical analyses, we show that mutations in genes associated with melanogenesis can profoundly alter the amount, shape, and arrangement of the melanin granules inside feathers that interact with light and produce iridescence. These changes can switch feather appearance between dull and iridescent, or generate entirely new colors by restructuring how those granules are layered at the microscopic scale. Our results reveal a direct and flexible link between pigment production and the physical structures that generate iridescence in birds.

evolutionary biology↗

Human Pumilio proteins use fuzzy multivalent hydrophobic interactions to recruit the CCR4-NOT deadenylase complex to repress mRNAs

Pumilio (PUM) proteins are conserved RNA-binding proteins that control mRNAs involved in development, proliferation, and stem cell differentiation. Human PUM1 and PUM2 repress targets by recruiting the CCR4-NOT deadenylase complex through a metazoan-specific N-terminal repression domain (RD3), which is predicted to be intrinsically disordered. Here we dissect RD3 using cell-based reporter assays, protein interaction assays with recombinant proteins, and crosslinking mass spectrometry. We identify multiple short RD3 peptides that are sufficient for repression and bind directly to the C-terminal NOT module of CCR4-NOT, comprising CNOT1, CNOT2, and CNOT3 subunits. Crosslinking reveals numerous mutually exclusive contacts between RD3 and the NOT module, consistent with a multivalent "fuzzy" binding mode in which interactions are not defined by a single sequence or structure. Sequence scrambling shows that the linear amino acid order of RD3 is dispensable, whereas its physicochemical composition, in particular distributed aliphatic and aromatic residues, is essential for repression and CCR4-NOT binding. These findings support a model in which low-affinity, multivalent interactions between intrinsically disordered regions (IDRs) and effector complexes, governed by amino acid composition rather than precise sequence, underlie robust PUM-mediated repression, and exemplify general principles by which IDRs recruit the CCR4-NOT complex to regulate gene expression. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=74 SRC="FIGDIR/small/695197v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@d4680aorg.highwire.dtl.DTLVardef@fa9c3dorg.highwire.dtl.DTLVardef@12783f7org.highwire.dtl.DTLVardef@148e657_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

molecular biology↗

A paradigm for regulation at the effector interface with RNA-binding proteins

RNA-binding proteins (RBPs) are key regulators of gene expression, but how RBPs convey regulatory instructions to the core effectors of RNA processing is unclear. Here we document the existence and functions of a multivalent RBP-effector interface. We show that the effector interface of a deeply conserved RBP with an essential role in metazoan development, Unkempt, is mediated by a novel type of dual-purpose peptide motifs that can contact two different surfaces of interacting proteins. Unexpectedly, we find that the multivalent contacts do not merely serve effector recruitment but are required for the accuracy of RNA recognition by the recruiting RBP. Systems analyses reveal that multivalent RBP-effector contacts can repurpose the principal activity of an effector for a different function, as we demonstrate for reuse of the central eukaryotic mRNA decay factor CCR4-NOT in translational control. Our study establishes the molecular assembly and functional principles of an RBP-effector interface, with implications for the evolution and function of RBP-operated regulatory networks.

molecular biology↗

Category representations in the primary visual cortex support orientation discrimination

Neuronal population activity in sensory cortices is the substrate for perceptual decisions. Yet, we still do not understand how neuronal information content in sensory cortices relates to behavioral reports. To reconcile neurometric and psychometric performance, we recorded the activity of V1 neurons in mice performing a Go/NoGo orientation discrimination task. We found that, around the discrimination threshold, V1 does not represent the orientation of the stimuli as canonically expected. Instead, it forms categorical representations characterized by a relocation of activity at task-relevant domains of the orientation representational space. The relative neuronal activity at those discrete domains accurately predicted the probabilities of the animals decisions. Our results thus suggest that the categorical integration of discretized feature representations from sensory cortices explains perceptual decisions.

neuroscience↗

Dynamic distortion of the orientation representational space after learning in the mouse primary visual cortex

Learning is an essential cognitive mechanism allowing behavioral adaptation through adjustments in neuronal processing. It is associated with changes in the activity of sensory cortical neurons evoked by task-relevant stimuli. However, the exact nature of those modifications and the computational advantages they may confer are still debated. Here, we investigated how learning an orientation discrimination task alters the neuronal representations of the cues orientations in the primary visual cortex (V1) of male and female mice. When comparing the activity evoked by the task stimuli in naive mice and mice performing the task, we found that the representations of the orientation of the rewarded and non-rewarded cues were more accurate and stable in trained mice. This better cue representation in trained mice was associated with a distortion of the orientation representation space such that stimuli flanking the task-relevant orientations were represented as the task stimuli themselves, suggesting that those stimuli were generalized as the task cues. This distortion was context dependent as it was absent in trained mice passively viewing the task cues and enhanced in the behavioral sessions where mice performed best. Those modifications of the V1 population orientation representation in performing mice were supported by a suppression of the activity of neurons tuned for orientations neighboring the orientations of the task cues. Thus, visual processing in V1 is dynamically adapted to enhance the reliability of the representation of the learned cues and favor generalization in the task-relevant computational space. Significance statementPerformance improvement in a task often requires facilitating the extraction of the information necessary to its execution. Here, we demonstrate the existence of a suppression mechanism that improves the representation of the orientations of the task stimuli in the V1 of mice performing an orientation discrimination task. We also show that this mechanism distorts the V1 orientation representation space, leading stimuli flanking the task stimuli orientations to be generalized as the task stimuli themselves.

neuroscience↗