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3 Publications

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    06/21/19 | High precision coding in visual cortex
    Stringer C, Michaelos M, Pachitariu M
    BioRxiv. 06/2019:679324. doi: https://doi.org/10.1101/679324

    Single neurons in visual cortex provide unreliable measurements of visual features due to their high trial-to-trial variability. It is not known if this “noise” extends its effects over large neural populations to impair the global encoding of sensory stimuli. We recorded simultaneously from ∼20,000 neurons in mouse visual cortex and found that the neural population had discrimination thresholds of 0.3° in an orientation decoding task. These thresholds are ∼100 times smaller than those reported behaviorally in mice. The discrepancy between neural and behavioral discrimination could not be explained by the types of stimuli we used, by behavioral states or by the sequential nature of trial-by-trial perceptual learning tasks. These results imply that the limits of sensory perception in mice are not set by neural noise in sensory cortex, but by the limitations of downstream decoders.

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    12/02/16 | Inhibitory control of correlated intrinsic variability in cortical networks
    Stringer C, Pachitariu M, Steinmetz NA, Okun M, Bartho P, Harris KD, Sahani M, Lesica NA
    Elife. 12/2016;5:e19695. doi: https://doi.org/10.7554/eLife.19695

    Cortical networks exhibit intrinsic dynamics that drive coordinated, large-scale fluctuations across neuronal populations and create noise correlations that impact sensory coding. To investigate the network-level mechanisms that underlie these dynamics, we developed novel computational techniques to fit a deterministic spiking network model directly to multi-neuron recordings from different rodent species, sensory modalities, and behavioral states. The model generated correlated variability without external noise and accurately reproduced the diverse activity patterns in our recordings. Analysis of the model parameters suggested that differences in noise correlations across recordings were due primarily to differences in the strength of feedback inhibition. Further analysis of our recordings confirmed that putative inhibitory neurons were indeed more active during desynchronized cortical states with weak noise correlations. Our results demonstrate that network models with intrinsically-generated variability can accurately reproduce the activity patterns observed in multi-neuron recordings and suggest that inhibition modulates the interactions between intrinsic dynamics and sensory inputs to control the strength of noise correlations.

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    03/03/14 | Simultaneous computation of dynamical and equilibrium information using a weighted ensemble of trajectories
    Suarez E, Lettieri S, Stringer CA, Zwier MC, Subramanian SR, Chong LT, Zuckerman DM
    Journal of Chemical Theory and Computation. 03/2014;10:2658–2667. doi: https://doi.org/10.1021/ct401065r

    Equilibrium formally can be represented as an ensemble of uncoupled systems undergoing unbiased dynamics in which detailed balance is maintained. Many nonequilibrium processes can be described by suitable subsets of the equilibrium ensemble. Here, we employ the “weighted ensemble” (WE) simulation protocol [Huber and Kim, Biophys. J.1996, 70, 97–110] to generate equilibrium trajectory ensembles and extract nonequilibrium subsets for computing kinetic quantities. States do not need to be chosen in advance. The procedure formally allows estimation of kinetic rates between arbitrary states chosen after the simulation, along with their equilibrium populations. We also describe a related history-dependent matrix procedure for estimating equilibrium and nonequilibrium observables when phase space has been divided into arbitrary non-Markovian regions, whether in WE or ordinary simulation. In this proof-of-principle study, these methods are successfully applied and validated on two molecular systems: explicitly solvated methane association and the implicitly solvated Ala4 peptide. We comment on challenges remaining in WE calculations.

     

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