bioRxiv ScienceSearch

bioRxiv · 10.1101/180125

A unifying motif for spatial and directional surround suppression

Abstract

In the visual system, the response to a stimulus in a neurons receptive field can be modulated by stimulus context, and the strength of these contextual influences vary with stimulus intensity. Recent work has shown how a theoretical model, the stabilized supralinear network (SSN), can account for such modulatory influences, using a small set of computational mechanisms. While the predictions of the SSN have been confirmed in primary visual cortex (V1), its computational principles apply with equal validity to any cortical structure. We have therefore tested the generality of the SSN by examining modulatory influences in the middle temporal area (MT) of the macaque visual cortex, using electrophysiological recordings and pharmacological manipulations. We developed a novel stimulus that can be adjusted parametrically to be larger or smaller in the space of all possible motion directions. We found, as predicted by the SSN, that MT neurons integrate across motion directions for low-contrast stimuli, but that they exhibit suppression by the same stimuli when they are high in contrast. These results are analogous to those found in visual cortex when stimulus size is varied in the space domain. We further tested the mechanisms of inhibition using pharmacologically manipulations of inhibitory efficacy. As predicted by the SSN, local manipulation of inhibitory strength altered firing rates, but did not change the strength of surround suppression. These results are consistent with the idea that the SSN can account for modulatory influences along different stimulus dimensions and in different cortical areas.\n\nSignificance StatementVisual neurons are selective for specific stimulus features in a region of visual space known as the receptive field, but can be modulated by stimuli outside of the receptive field. The SSN model has been proposed to account for these and other modulatory influences, and tested in V1. As this model is not specific to any particular stimulus feature or brain region, we wondered whether similar modulatory influences might be observed for other stimulus dimensions and other regions. We tested for specific patterns of modulatory influences in the domain of motion direction, using electrophysiological recordings from MT. Our data confirm the predictions of the SSN in MT, suggesting that the SSN computations might be a generic feature of sensory cortex.

Source connections

Explore related subjects

Keep this discovery

BibTeXRIS

Liu, L. D., Miller, K. D., Pack, C. C.. 2017-08-24. A unifying motif for spatial and directional surround suppression. https://doi.org/10.1101/180125

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience