Search bioRxiv⌕ Search

bioRxiv · 10.1101/2024.01.30.577979

Cortical multi-area model with joint excitatory-inhibitory clusters accounts for spiking statistics, inter-area propagation, and variability dynamics

Abstract

The primate brain uses billions of interacting neurons to produce macroscopic dynamics and behavior, but current methods only allow neuroscientists to investigate a subset of the neural activity. Computational modeling offers an alternative testbed for scientific hypotheses, by allowing full control of the system. Here, we test the hypothesis that local cortical circuits are organized into joint clusters of excitatory and inhibitory neurons by investigating the influence of this organizational principle on cortical resting-state spiking activity, inter-area propagation, and variability dynamics. The model represents all vision-related areas in one hemisphere of the macaque cortex with biologically realistic neuron densities and connectivities, expanding on a previous unclustered model of this system. Each area is represented by a square millimeter microcircuit including the full density of neurons and synapses, avoiding downscaling artifacts and testing cortical dynamics at the natural scale. We find that joint excitatory-inhibitory clustering normalizes spiking activity statistics in terms of firing rate distributions and inter-spike interval variability. A comparison with data from cortical areas V1, V4, FEF, 7a, and DP shows that the clustering enables the resting-state activity of especially higher cortical areas to be better captured. In addition, we find that the clustering supports signal propagation across all areas in both feedforward and feedback directions with reasonable latencies. Finally, we also show that localized stimulation of the clustered model quenches the variability of neural activity, in agreement with experimental observations. We conclude that joint clustering of excitatory and inhibitory neurons is a likely organizational principle of local cortical circuits, supporting resting-state spiking activity statistics, inter-area propagation, and variability dynamics.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Pronold, J., Morales-Gregorio, A., Rostami, V., van Albada, S. J.. 2024-01-30. Cortical multi-area model with joint excitatory-inhibitory clusters accounts for spiking statistics, inter-area propagation, and variability dynamics. https://doi.org/10.1101/2024.01.30.577979

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

KEEP EXPLORING

Related preprints

A Mechanistic Account of Dedifferentiation in the Aging Visual System

To uncover the mechanisms of age-related dedifferentiation, we simulated neural degradation in a computational model of the ventral visual stream. Severing connections or adding noise, whether in inferotemporal cortex (IT) or upstream, reduced IT differentiation, indicating that dedifferentiation need not originate locally. Degrading peripheral V1, which preferentially drove place-selective IT neurons, selectively reduced place differentiation, a candidate mechanism for the stronger place dedifferentiation reported in aging.

neuroscience↗

Reusing pipettes in Patch-seq: a foundation for automated multimodal profiling

Patch-seq is a technique for single-cell multimodal characterization. It combines whole-cell electrophysiology, single-cell transcriptomics, and morphological reconstruction in single neurons. Patch-seq morphologies are a critical bridge among cell types, genes, physiology, and large-scale connectivity platforms such as EM connectomes and single-cell-resolution projectomes. However, patch-seq experimental complexity and operator dependence limit throughput. Automation could enable scalable Patch-seq but requires procedural adaptations, including detergent-based pipette cleaning, robotic nucleus extraction and collection. The impact of these automations on Patch-seq quality has not been systematically evaluated. Here, we show that each of these modifications preserves or improves key Patch-seq outcomes. Automated nucleus extraction performs comparably to, or better than, expert manual operation, preserving key RNA and morphological metrics. Detergent-cleaned, reused pipettes supported a viable sealing success rate across multiple cleaning cycles and preserved electrophysiological quality and transcriptomic yield without introducing excess contamination. Sonication effectively allows collection of nuclear material without damaging RNA and supports subsequent pipette cleaning and reuse. Enhanced automated sealing and break-in procedures increased throughput regardless of brain region, cell type or species. Together, these results validate the core procedural adaptations required for automated Patch-seq and establish a foundation for high-throughput, standardized multimodal single-cell characterization.

neuroscience↗

Development of direction selectivity in the Xenopus tadpole optic tectum and midbrain tegmentum

Detecting motion direction is a fundamental function performed by direction selective (DS) neurons. DS neurons in the optic tectum (superior colliculus in mammals) enable the tracking of moving objects. DS neurons of the accessory optic system support reflexive eye / head movements that stabilize gaze during self-motion. By developmental stage 48 (10 days postfertilization), Xenopus tadpoles display visually guided behaviors that require both types of DS neurons. Our previous work has shown that these two regions are not only functionally distinct but also follow different developmental programs. Here we characterized and compared how direction selectivity develops in both visual processing centers. Using in vivo electrophysiological recordings during moving bar visual stimulation, we measured DS synaptic inputs and spiking outputs in both regions across three key developmental stages of the retinotectal projection. Tegmental neurons were direction selective ab initio, and both input and output tuning remained stable across development. Tectal neurons were observed to receive DS inputs early, and their input selectivity also remained stable across development. However, their spiking output grew substantially more DS at the later developmental stage. This was due at least in part to a naturally occurring decrease in intrinsic excitability which preferentially dampened overall spike rates, but especially in response to the non-preferred direction of motion, thereby increasing direction selectivity. These results reveal distinct developmental trajectories in parallel visual pathways. Tegmental direction selectivity is established early and stays stable, whereas tectal output tuning sharpens during development through a decrease in intrinsic excitability.

neuroscience↗