bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.04.21.590492

Quantitative Analysis of Roles of Direct and Indirect Pathways for Action Selection in The Basal Ganglia

Abstract

We are concerned about action selection in the basal ganglia (BG). We quantitatively analyze functions of direct pathway (DP) and indirect pathway (IP) for action selection in a spiking neural network with 3 competing channels. For such quantitative analysis, in each channel, we obtain the competition degree [C]d, given by the ratio of strength of DP ([S]DP) to strength of IP ([S]IP) (i.e., [C]d = [S]DP /[S]IP). Then, a desired action is selected in the channel with the largest [C]d. Desired action selection is made mainly due to strong focused inhibitory projection to the output nucleus, SNr (substantia nigra pars reticulata) via the DP in the corresponding channel. Unlike the case of DP, there are two types of IPs; intra-channel IP and inter-channel IP, due to widespread diffusive excitation from the STN (subthalamic nucleus). The intra-channel IP serves a function of brake to suppress the desired action selection. In contrast, the inter-channel IP to the SNr in the neighboring channels suppresses competing actions, leading to highlight the desired action selection. In this way, function of the inter-channel IP is opposite to that of the intra-channel IP. However, to the best of our knowledge, no quantitative analysis for such functions of the DP and the two IPs was made. Here, through direct calculations of the DP and the intra- and the inter-channel IP presynaptic currents into the SNr in each channel, we obtain the competition degree of each channel to determine a desired action, and then functions of the DP and the intra- and inter-channel IPs are quantitatively made clear. PACS numbers87.19.lj, 87.19.lu, 87.19.rs

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kim, S.-Y., Lim, W.. 2024-04-23. Quantitative Analysis of Roles of Direct and Indirect Pathways for Action Selection in The Basal Ganglia. https://doi.org/10.1101/2024.04.21.590492

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↗