CONNECTOME-CONSTRAINED LATENT VARIABLE MODELS OF WHOLE-BRAIN NEURAL ACTIVITY

Lu Mi, Richard Xu, Sridhama Prakhya, Albert Lin, Nir Shavit, Aravinthan D.T. Samuel, Srinivas C. Turaga

Research output: Contribution to conferencePaperpeer-review

Abstract

The availability of both anatomical connectivity and brain-wide neural activity measurements in C. elegans make the worm a promising system for learning detailed, mechanistic models of an entire nervous system in a data-driven way. However, one faces several challenges when constructing such a model. We often do not have direct experimental access to important modeling details such as single-neuron dynamics and the signs and strengths of the synaptic connectivity. Further, neural activity can only be measured in a subset of neurons, often indirectly via calcium imaging, and significant trial-to-trial variability has been observed. To address these challenges, we introduce a connectome-constrained latent variable model (CC-LVM) of the unobserved voltage dynamics of the entire C. elegans nervous system and the observed calcium signals. We used the framework of variational autoencoders to fit parameters of the mechanistic simulation constituting the generative model of the LVM to calcium imaging observations. A variational approximate posterior distribution over latent voltage traces for all neurons is efficiently inferred using an inference network, and constrained by a prior distribution given by the biophysical simulation of neural dynamics. We applied this model to an experimental whole-brain dataset, and found that connectomic constraints enable our LVM to predict the activity of neurons whose activity were withheld significantly better than models unconstrained by a connectome. We explored models with different degrees of biophysical detail, and found that models with realistic conductance-based synapses provide markedly better predictions than current-based synapses for this system.

Original languageEnglish
StatePublished - 2022
Externally publishedYes
Event10th International Conference on Learning Representations, ICLR 2022 - Virtual, Online
Duration: 25 Apr 202229 Apr 2022

Conference

Conference10th International Conference on Learning Representations, ICLR 2022
CityVirtual, Online
Period25/04/2229/04/22

Funding

FundersFunder number
National Institutes of Health1 U01 NS111697-01
Howard Hughes Medical Institute
Intel Corporation
MathWorksIOS-1555914, NSF 1806818

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