Metamodelling of a two-population spiking neural network.

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 parameter values 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 and compare two different metamodelling techniques, masked autoregressive flows (MAF) and deep Gaussian process regression (DGPR), 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, and that the DGPR metamodel provides a more accurate representation of the simulator compared to the MAF metamodel. Using the metamodels, we estimate the posterior probability distributions over parameters given observed simulator outputs separately for both LFP and population spiking activities. We find that these distributions correctly identify parameter combinations that give similar model outputs, and that some parameters are significantly more constrained by observing the LFP than by observing the population spiking activities.

Uncovering circuit mechanisms of current sinks and sources with biophysical simulations of primary visual cortex.

Local field potential (LFP) recordings reflect the dynamics of the current source density (CSD) in brain tissue. The synaptic, cellular, and circuit contributions to current sinks and sources are ill-understood. We investigated these in mouse primary visual cortex using public Neuropixels recordings and a detailed circuit model based on simulating the Hodgkin-Huxley dynamics of >50,000 neurons belonging to 17 cell types. The model simultaneously captured spiking and CSD responses and demonstrated a two-way dissociation: firing rates are altered with minor effects on the CSD pattern by adjusting synaptic weights, and CSD is altered with minor effects on firing rates by adjusting synaptic placement on the dendrites. We describe how thalamocortical inputs and recurrent connections sculpt specific sinks and sources early in the visual response, whereas cortical feedback crucially alters them in later stages. These results establish quantitative links between macroscopic brain measurements (LFP/CSD) and microscopic biophysics-based understanding of neuron dynamics and show that CSD analysis provides powerful constraints for modeling beyond those from considering spikes.

RippleNet: a Recurrent Neural Network for Sharp Wave Ripple (SPW-R) Detection.

Hippocampal sharp wave ripples (SPW-R) have been identified as key bio-markers of important brain functions such as memory consolidation and decision making. Understanding their underlying mechanisms in healthy and pathological brain function and behaviour rely on accurate SPW-R detection. In this multidisciplinary study, we propose a novel, self-improving artificial intelligence (AI) detection method in the form of deep Recurrent Neural Networks (RNN) with Long Short-Term memory (LSTM) layers that can learn features of SPW-R events from raw, labeled input data. The approach contrasts conventional routines that typically relies on hand-crafted, heuristic feature extraction and often laborious manual curation. The algorithm is trained using supervised learning on hand-curated data sets with SPW-R events obtained under controlled conditions. The input to the algorithm is the local field potential (LFP), the low-frequency part of extracellularly recorded electric potentials from the CA1 region of the hippocampus. Its output predictions can be interpreted as time-varying probabilities of SPW-R events for the duration of the inputs. A simple thresholding applied to the output probabilities is found to identify times of SPW-R events with high precision. The non-causal, or bidirectional variant of the proposed algorithm demonstrates consistently better accuracy compared to the causal, or unidirectional counterpart. Reference implementations of the algorithm, named 'RippleNet', are open source, freely available, and implemented using a common open-source framework for neural networks (tensorflow.keras) and can be easily incorporated into existing data analysis workflows for processing experimental data.

Brain Modeling ToolKit: An open source software suite for multiscale modeling of brain circuits.

Experimental studies in neuroscience are producing data at a rapidly increasing rate, providing exciting opportunities and formidable challenges to existing theoretical and modeling approaches. To turn massive datasets into predictive quantitative frameworks, the field needs software solutions for systematic integration of data into realistic, multiscale models. Here we describe the Brain Modeling ToolKit (BMTK), a software suite for building models and performing simulations at multiple levels of resolution, from biophysically detailed multi-compartmental, to point-neuron, to population-statistical approaches. Leveraging the SONATA file format and existing software such as NEURON, NEST, and others, BMTK offers a consistent user experience across multiple levels of resolution. It permits highly sophisticated simulations to be set up with little coding required, thus lowering entry barriers to new users. We illustrate successful applications of BMTK to large-scale simulations of a cortical area. BMTK is an open-source package provided as a resource supporting modeling-based discovery in the community.

Estimation of neural network model parameters from local field potentials (LFPs).

Most modeling in systems neuroscience has been descriptive where neural representations such as 'receptive fields', have been found by statistically correlating neural activity to sensory input. In the traditional physics approach to modelling, hypotheses are represented by mechanistic models based on the underlying building blocks of the system, and candidate models are validated by comparing with experiments. Until now validation of mechanistic cortical network models has been based on comparison with neuronal spikes, found from the high-frequency part of extracellular electrical potentials. In this computational study we investigated to what extent the low-frequency part of the signal, the local field potential (LFP), can be used to validate and infer properties of mechanistic cortical network models. In particular, we asked the question whether the LFP can be used to accurately estimate synaptic connection weights in the underlying network. We considered the thoroughly analysed Brunel network comprising an excitatory and an inhibitory population of recurrently connected integrate-and-fire (LIF) neurons. This model exhibits a high diversity of spiking network dynamics depending on the values of only three network parameters. The LFP generated by the network was computed using a hybrid scheme where spikes computed from the point-neuron network were replayed on biophysically detailed multicompartmental neurons. We assessed how accurately the three model parameters could be estimated from power spectra of stationary 'background' LFP signals by application of convolutional neural nets (CNNs). All network parameters could be very accurately estimated, suggesting that LFPs indeed can be used for network model validation.