bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.08.19.608588

CA1 ensemble plasticity is coupled to context change and modulated by task familiarity

Abstract

When should plasticity mechanisms get recruited (stability-plasticity dilemma)? Environments change over time, re/entering a given context increases uncertainty and predicts the need for updating. Hippocampus (HPC) is key to tracking context change but also navigation in relation to moving targets. CA1 ensembles expressing immediate-early genes (IEGs) are contextually specific, while the amount of IEG expression correlates with HPC-dependent task demands. However, task effects on the IEG-expressing ensembles per se remain unclear. In three experiments, we tested the effect of context change and HPC task demands on CA1 IEG+ ensembles in rats. Experiment 1 showed that the IEG+ (Arc, Homer1a RNA) ensemble size drops to baseline level during uninterrupted 30 min exploration, reflecting familiarization and decreasing uncertainty, unless context change is present; the ensemble sizes reflect both context identity and context change. Experiment 2 showed no evidence of task-specificity of IEG+ ensembles during highly HPC-dependent mobile robot avoidance nor HPC-independent stationary robot avoidance. Experiment 3 replicated the findings of Experiment 2 for c-Fos protein. Nonetheless, the data suggest that ensembles shrink with task mastery/familiarity and grow with novelty presented by acquisition of behavioral extinction. Overall, our results shed light on the temporal dynamics, and the context and task control of CA1 IEG+ ensembles. The present results and the relevant literature suggest that context change resets the ensemble of IEG-expressing CA1 neurons and novelty delays the time-dependent ensemble shrinking. HIGHLIGHTSO_LIPlasticity and learning rate should reflect novelty and familiarity, i.e. uncertainty C_LIO_LIChange of context and task requirements increase uncertainty C_LIO_LIFamiliarization with context and task reduces uncertainty C_LIO_LIFor context, this pattern is matched by dynamics of IEG+ ensembles in CA1 C_LIO_LITask demands have modulating influence on CA1 IEG+ ensembles C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/608588v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@12808c0org.highwire.dtl.DTLVardef@156ad3corg.highwire.dtl.DTLVardef@1876f0aorg.highwire.dtl.DTLVardef@8b13f4_HPS_FORMAT_FIGEXP M_FIG C_FIG

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Krajcovic, B., Cernotova, D., Stuchlik, A., Kubik, S., Svoboda, J.. 2024-08-19. CA1 ensemble plasticity is coupled to context change and modulated by task familiarity. https://doi.org/10.1101/2024.08.19.608588

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↗