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Acosta, F.

Publications and source records attributed to Acosta, F..

3 recordsLinked to original sources

A geometric and dynamical theory of latent computations in biological neural networks

Many neural recordings have revealed low-dimensional sets of behaviorally relevant variables encoded within large-scale neural activity patterns. However, dimensionality reduction analyses alone cannot yield causal explanations for how networks stably implement computations that are resilient to the substantial variability of single neuron dynamics. Further, existing methods for dimensionality reduction often rely on simplifying assumptions about network structure that limit their applicability and explanatory power. To provide a theoretical framework describing the dynamics of low-dimensional computation in high-dimensional neural networks, here we introduce the concept of latent processing units (LPUs), which are architecture-agnostic computational elements operating within biological neural circuitry. Six theorems governing coding and computation by LPUs collectively provide explanations for a range of common biological findings: low-dimensional sets of coding variables can generate high-dimensional neural dynamics; many neurons have activity patterns that represent behaviorally relevant variables but exert little influence on downstream circuits; linear readouts of neural population activity commonly permit near-optimal decoding; the drift of neural representations is often substantial even while network computations remain intact. Overall, our treatment of LPUs, as enacted in network dynamics, unifies the geometric and dynamical views of neural computation under a joint framework and provides systems neuroscience with a causal account of how the brain executes reliable computations.

neuroscience↗

A Cluster of Acidic Residues in the Cytoplasmic Domain of SARS-CoV-2 Spike is Required for Virion-Incorporation and Infectivity

Abstract/SummaryLike all coronaviruses, the infectivity of SARS-CoV-2 virus particles (virions) requires incorporation of the Spike glycoprotein. Yet, the mechanisms that support the virion-incorporation of Spike are incompletely defined. We noted an unusual feature of human sarbecovirus Spike proteins: their cytoplasmic domains (CDs) contain a stretch of acidic amino acids (DEDDSE). This sequence resembles a cluster of acidic residues, or acidic cluster (AC) motif, found in the cytoplasmic domain of the cellular endoprotease Furin. In Furin, the acidic cluster acts as a protein sorting signal, supporting its intracellular localization at the trans-Golgi network (TGN). We tested the contribution of the acidic cluster motif in the Spike CD to protein interactions and to the infectivity of SARS-CoV-2. We used virus-like particles (VLPs) as a model for viral "infection" (transduction). The SARS-CoV2 VLPs were produced by co-expressing Spike (S), Membrane (M), Envelope (E) and Nucleocapsid (N) proteins and deliver an RNA encoding luciferase to target cells expressing the ACE2 receptor. Remarkably, when all five acidic residues of the DEDDSE sequence were replaced with alanines, the VLPs were rendered non-infectious. The N-terminal DE residues provided most of the activity of the acidic cluster. These virologi-cally-impaired Spike mutants were able to reach the cell surface and induce the formation of syncytia, indicating that they are fusogenic and capable of anterograde traffic through the biosynthetic pathway to the plasma membrane. Despite this, they failed to efficiently incorporate into virions. We observed acidic cluster motif-dependent interactions of the Spike CD with several cellular proteins that could potentially support its role in virion-incorporation, including the ERM proteins Ezrin, Radixin, and Moesin; the retromer subunit Vps35, and the medium subunits of the clathrin adaptor complexes AP1 and AP2. While the key cofactor and mechanism of action remains to be defined, this region of acidic residues in the Spike CD appears to be a novel determinant of SARS-CoV-2 infectivity.

molecular biology↗

Not so griddy: Internal representations of RNNs path integrating more than one agent

Success in collaborative and competitive environments, where agents must work with or against each other, requires individuals to encode the position and trajectory of themselves and others. Decades of neurophysiological experiments have shed light on how brain regions [e.g., medial entorhinal cortex (MEC), hippocampus] encode the selfs position and trajectory. However, it has only recently been discovered that MEC and hippocampus are modulated by the positions and trajectories of others. To understand how encoding spatial information of multiple agents shapes neural representations, we train a recurrent neural network (RNN) model that captures properties of MEC to path integrate trajectories of two agents simultaneously navigating the same environment. We find significant differences between these RNNs and those trained to path integrate only a single agent. At the individual unit level, RNNs trained to path integrate more than one agent develop weaker grid responses, stronger border responses, and tuning for the relative position of the two agents. At the population level, they develop more distributed and robust representations, with changes in network dynamics and manifold topology. Our results provide testable predictions and open new directions with which to study the neural computations supporting spatial navigation.

neuroscience↗