bioRxiv Science⌕ Search

bioRxiv · 10.1101/2022.09.05.506616

Metamodelling of a two-population spiking neural network

Abstract

In computational neuroscience, hypotheses are often formulated as bottom-up mechanistic models of the systems in question, consisting of differential equations that can be numerically integrated forward in time. Candidate models can then be validated by comparison against experimental data. The model outputs of neural network models depend on both neuron parameters, connectivity parameters and other model inputs. Successful model fitting requires sufficient exploration of the model parameter space, which can be computationally demanding. Additionally, identifying degeneracy in the parameters, i.e. different combinations of parameter values that produce similar outputs, is of interest, as they define the subset of models consistent with the data. In this computational study, we apply metamodels to a two-population recurrent spiking network of point-neurons, the so-called Brunel network. Metamodels are data-driven approximations to more complex models with more desirable computational properties, which can be run considerably faster than the original model. Specifically, we apply two different metamodelling techniques, Masked Autoregressive Flows and Deep Gaussian Process Regression, to estimate the power spectra of two different signals; the population spiking activities and the local field potential. We find that the metamodels are able to accurately model the power spectra in the asynchronous irregular regime. Using the metamodels, we invert the network, and estimate the probability distributions over parameters that can give rise to observed simulation outputs. We find that these distributions correctly identify parameter combinations that give similar model outputs, and that the parameters are constrained to different degrees by observing the two different signals. Author summaryIn computational neuroscience, mechanistic models are used to simulate networks of neurons. These models exhibit complex dynamics, and the parameters of the neurons and connections between neurons shape the models behaviour. Due to the model complexity, running the simulations and fitting the model to experimental data can be computationally demanding. In this study, we apply metamodelling techniques, data-driven approximations that are much faster to run, to two different signals generated by a two-population recurrent network model, the population spiking activities and the local field potential (LFP). Further, we invert the metamodels, and demonstrate that it can reliably find the different combinations of parameters that can give rise to an observed simulation output. We compare the metamodels on both the forward and inverse problem, and investigate to what degree the parameters are constrained by the two different signals.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Skaar, J.-E. W., Stasik, A. J., Plesser, H. E., Einevoll, G. T., Tondel, K.. 2022-09-06. Metamodelling of a two-population spiking neural network. https://doi.org/10.1101/2022.09.05.506616

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

KEEP EXPLORING

Related preprints

Epidermal Langerhans Cells Act as Neuroimmune Regulators of Pain and Itch

Neuroimmune interactions in the skin coordinate immune defense and somatosensory perception, yet how immune cells shape sensory signaling remains poorly defined. Here, we show that Langerhans cells (LCs), epidermal antigen-presenting cells, function as local immune-derived amplifiers of cutaneous sensory signaling. Anatomical and transcriptomic analyses reveal preferential LC association with non-peptidergic sensory neurons. LC activation increases neuronal and behavioral responses to thermal, mechanical, and pruritic stimuli without directly exciting sensory neurons, whereas LC inhibition or ablation selectively reduces pruritogen-evoked itch. We identified semaphorin 7A as a candidate LC-expressed mediator. Semaphorin 7A sensitized cultured sensory neurons to chloroquine and histamine, and neutralizing semaphorin 7A abolished the increase in chloroquine-evoked scratching produced by LC activation. Its receptor PlexinC1 was expressed by most MrgprA3 pruriceptors and blocking PlexinC1 reduced semaphorin 7A-evoked neuronal responses. Together, these findings identify epidermal LCs as local immune-derived amplifiers that regulate the responsiveness of cutaneous sensory circuits and identify semaphorin 7A as a mediator of LC-induced itch potentiation.

neuroscience↗

Feasible closed-loop stimulation for neural latent dynamics control

Modern neuroscience benefits from powerful computational and experimental methods for studying neural populations, including latent dynamics models that predict behavior with few dimensions. But despite their explanatory utility, latent factors are seldom targeted explicitly with experimental perturbations, leaving causal relationships to behavior and inferred dynamical landscapes untested. A promising solution is closed-loop, multi-channel optogenetic control, which, when paired with model predictions, could steer neural trajectories in real time--a feat impossible for traditional, hand-designed stimulation. However, because closed-loop latent control has not been demonstrated in vivo, the hardware and software requirements remain unclear--particularly the necessary stimulation dimensionality and how limited resources such as implant volume and bandwidth should be allocated between stimulation and recording capabilities. Preliminary experiments would thus help guide ongoing technological development. As large-scale exploration of these design spaces in vivo is prohibitively expensive, we conducted a high-throughput simulation survey using biophysically grounded spiking neural networks. We found that low-dimensional actuation is sufficient: in the reference configuration, ~20% of the stimulation channels achieved ~85% of peak control performance, far fewer than the number of neurons. Furthermore, allocating channels roughly equally between stimulation and recording optimized behavioral control, whereas pairing many electrodes with a single light source--the prevailing practice in experimental labs--performed poorly. Even without heavily optimizing modeling or control, we obtained >60% tracking error reduction and >90% evoked behavior accuracy on average for optimal channel counts. These results held across extensive parameter variations, suggesting that closed-loop latent control is feasible with accessible channel counts and establishing design principles for future tool development and in vivo experiments.

neuroscience↗

Identification of Kinome Biomarkers and Therapeutic Rescue in cGMP-Linked Retinal Degeneration

Inherited retinal degenerations, such as Retinitis Pigmentosa (RP) and Leber's congenital amaurosis (LCA), are major causes of progressive and irreversible vision loss. The large number of genes associated with these disorders makes their clinical and molecular characterization difficult, while systemic biomarkers for disease progression or treatment response remain limited. These challenges were addressed by targeting cGMP-associated mechanisms shared by RP and LCA and integrating systemic biomarker profiling with retinal outcomes. Kinase activity analysis (kinome analysis) in peripheral blood mononuclear cells distinguished healthy and diseased states and captured therapy-associated signatures in rd10 mice treated with LP-CN03, a liposomal formulation of the cGMP analog CN03. This first systemic analysis in a therapeutically responsive animal model highlights kinome analysis as a potential translational readout. Given shared cGMP signaling in RP and AIPL1-associated LCA, LP-CN03's therapeutic potential was further evaluated in a new CRISPR-Cas9-generated Aipl1-/- mouse model. Treatment with LP-CN03 preserved retinal structure and function, as shown by electroretinography, longitudinal optical coherence tomography, fundus imaging, optomotor testing, and photoreceptor-specific gene expression. Together, these findings provide independent in vivo evidence for the neuroprotective effect of LP-CN03 in both cGMP-related RP and LCA, also highlighting the translational value of kinome profiling.

neuroscience↗