Efficient "Shotgun" Inference of Neural Connectivity from Highly Sub-sampled Activity Data

PLoS Comput Biol. 2015 Oct 14;11(10):e1004464. doi: 10.1371/journal.pcbi.1004464. eCollection 2015 Oct.

Abstract

Inferring connectivity in neuronal networks remains a key challenge in statistical neuroscience. The "common input" problem presents a major roadblock: it is difficult to reliably distinguish causal connections between pairs of observed neurons versus correlations induced by common input from unobserved neurons. Available techniques allow us to simultaneously record, with sufficient temporal resolution, only a small fraction of the network. Consequently, naive connectivity estimators that neglect these common input effects are highly biased. This work proposes a "shotgun" experimental design, in which we observe multiple sub-networks briefly, in a serial manner. Thus, while the full network cannot be observed simultaneously at any given time, we may be able to observe much larger subsets of the network over the course of the entire experiment, thus ameliorating the common input problem. Using a generalized linear model for a spiking recurrent neural network, we develop a scalable approximate expected loglikelihood-based Bayesian method to perform network inference given this type of data, in which only a small fraction of the network is observed in each time bin. We demonstrate in simulation that the shotgun experimental design can eliminate the biases induced by common input effects. Networks with thousands of neurons, in which only a small fraction of the neurons is observed in each time bin, can be quickly and accurately estimated, achieving orders of magnitude speed up over previous approaches.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Animals
  • Computer Simulation
  • Connectome / methods*
  • Data Interpretation, Statistical
  • Humans
  • Models, Neurological*
  • Models, Statistical*
  • Nerve Net / physiology*
  • Neurons / physiology*
  • Sample Size
  • Synaptic Transmission / physiology*

Grants and funding

The work of DS was supported by the Gruss Lipper Charitable Foundation (http://www.eglcf.org). The work of LS was supported by 1) The army Research Office Multidisciplinary University Research Initiative W911NF-12-1-0594 (http://www.arl.army.mil/www/default.cfm?page=472), 2) The Defense Advanced Research Projects Agency W91NF-14-1-0269 and N66001-15-C-4032 (http://www.darpa.mil) 3) The National Science Foundation Faculty Early Career Development Program IOS-0641912 (http://www.nsf.gov) 4) The National Science Foundation IIS-1430239 (http://www.nsf.gov). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.