Multiscale model of primary motor cortex circuits predicts in vivo cell-type-specific, behavioral state-dependent dynamics

Durá-Bernal, Salvador; Neymotin, Samuel A.; Suter, Benjamin A.; Dacre, Joshua; Moreira, João Vitor da Silva; Urdapilleta, Eugenio; Schiemann, Julia; Duguid, Ian; Shepherd, Gordon M.; Lytton, William W.

doi:10.1016/j.celrep.2023.112574

Cited by 8 publications

(3 citation statements)

References 151 publications

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“…Furthermore, we were able to examine the spiking activity of each population during each oscillation event, mirroring multiunit activity from neurophysiological recordings, but with enhanced cell-type specificity. As LFP/CSD signals predominantly originate from synaptic transmembrane currents, we adapted an existing method 62 to estimate the cell-type-specific synaptic inputs driving the different populations and the oscillatory patterns within these inputs. This facilitates predictions about the most likely biophysical sources of LFP/CSD oscillatory events in terms of the oscillatory synaptic inputs generating them.…”

Section: Resultsmentioning

confidence: 99%

“…Generating physiologically constrained firing rates in all model populations required parameter tuning (also referred to as parameter fitting or optimization) of the connection strengths within biologically realistic ranges. Compared to our previous motor cortex model, 62 , 71 this process was particularly challenging in the non-human primate auditory system model and required developing and iteratively improving our automated parameter optimization methods. We believe the reasons for this include the addition of two inhibitory cell types (VIP and NGF) and the incorporation of thalamic circuitry, which resulted in complex recurrent intracortical and thalamocortical interactions.…”

Section: Discussionmentioning

confidence: 99%

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Data-driven multiscale model of macaque auditory thalamocortical circuits reproduces in vivo dynamics

Dura-Bernal,

Griffith,

Barczak

et al. 2023

Cell Reports

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Data-driven multiscale model of macaque auditory thalamocortical circuits reproduces in vivo dynamics

Dura-Bernal,

Griffith,

Barczak

et al. 2023

Cell Reports

Self Cite

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“…They find a single activity state, instead of the in vivo-compatible spectrum here that allowed us to contrast anesthetized and awake states. The model in general differs from hybrid models, which jointly use biologically-detailed models and point neuron models (Billeh et al, 2020;Dura-Bernal et al, 2023), and also from the work of Egger et al (2020) who modeled activation of L5 pyramidal cells by constraining patterns of synaptic input based on receptive fields and predicted anatomical innervation.…”

Section: Discussionmentioning

confidence: 99%

Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part II: Physiology and Experimentation

Isbister,

Ecker,

Pokorny

et al. 2023

Preprint

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In recent years, large-scale computational models of the cortex have emerged as a powerful way to study the multi-scale mechanisms of neural processing. However, due to computational costs and difficulty of parameterization, detailed biophysical reconstructions have so far been restricted to small volumes of tissue, where the study of macro- and meso-scale interactions that are central to cortical function is not possible. We describe here, and in a companion paper, an approach to address the scaling challenges and provide a model of multiple interacting cortical regions at a subcellular level of detail. The model consists of 4.2 million morphologically detailed neurons in 8 sub-regions and connected with 13.2 billion synapses through local and long-range connectivity. Its anatomical aspects are described in the companion paper; here, we introduce physiological models of neuronal activity and synaptic transmission that integrate a large number of literature sources and were built using previously published algorithms. Biological neuronal diversity was captured in 208 morpho-electrical neuron types, five types of synaptic short-term dynamics, and pathway-specificity of synaptic parameters. A representation of synaptic input from cortical regions not present in the model was added and efficiently calibrated to reference firing rates. The model exhibits a spectrum of dynamical states differing in the degree to which they are internally versus externally driven. We characterized which parts of the spectrum are compatible with available experimental data on layer-specific delays and amplitudes of responses to simple stimuli, and found anin vivo-like regime at the edge of a transition from asynchronous to synchronous spontaneous activity. We developed a rich set of simulation tools to recreate a diverse set of laboratory experimentsin silico, providing further validation and demonstrating the utility of the model in a variety of paradigms. Finally, we found that the large spatial scale of the model, that incorporates multiple cortical regions, led to the emergence of multiple independent computational units interacting through long-range synaptic pathways. The model provides a framework for the continued integration of experimental findings, for challenging hypotheses and making testable predictions, and provides a foundation for further simulation-based studies of cortical processing and learning.

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Data-driven multiscale computational models of cortical and subcortical regions

Ramaswamy

2024

Current Opinion in Neurobiology

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Multiscale model of primary motor cortex circuits predicts in vivo cell-type-specific, behavioral state-dependent dynamics

Cited by 8 publications

References 151 publications

Data-driven multiscale model of macaque auditory thalamocortical circuits reproduces in vivo dynamics

Data-driven multiscale model of macaque auditory thalamocortical circuits reproduces in vivo dynamics

Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part II: Physiology and Experimentation

Data-driven multiscale computational models of cortical and subcortical regions

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