bioRxiv Science⌕ Search

bioRxiv · 10.1101/2021.06.28.450144

Sparse connectivity for MAP inference in linear models using sister mitral cells

Abstract

Sensory processing is hard because the variables of interest are encoded in spike trains in a relatively complex way. A major goal in studies of sensory processing is to understand how the brain extracts those variables. Here we revisit a common encoding model in which variables are encoded linearly. Although there are typically more variables than neurons, this problem is still solvable because only a small number of variables appear at any one time (sparse prior). However, previous solutions require all-to-all connectivity, inconsistent with the sparse connectivity seen in the brain. Here we propose an algorithm that provably reaches the MAP (maximum a posteriori) inference solution, but does so using sparse connectivity. Our algorithm is inspired by the circuit of the mouse olfactory bulb, but our approach is general enough to apply to other modalities. In addition, it should be possible to extend it to nonlinear encoding models. SummarySensory systems must infer latent variables from noisy and ambiguous input. MAP inference - choosing the most likely latent variable given the sensory input - is one of the simplest methods for doing that, but its neural implementation often requires all-to-all connectivity between the neurons involved. In common sensory contexts this can require a single neuron to connect to hundreds of thousands of others, which is biologically implausible. In this work we take inspiration from the sister mitral cells of the olfactory system - groups of neurons associated with the same input channel - to derive a method for performing MAP inference using sparse connectivity. We do so by assigning sister cells to random subsets of the latent variables and using additional cells to ensure that sisters correctly share information. We then derive the circuitry and dynamics required for the sister cells to compute the original MAP inference solution. Our work yields a biologically plausible circuit that provably solves the MAP inference problem and provides experimentally testable predictions. While inspired by the olfactory system, our method is quite general, and is likely to apply to other sensory modalities.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Tootoonian, S., Schaefer, A. T., Latham, P. E.. 2021-06-28. Sparse connectivity for MAP inference in linear models using sister mitral cells. https://doi.org/10.1101/2021.06.28.450144

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↗