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

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.Author Summary: Optical imaging of the activity in a neuronal network is limited by the scanning speed of the imaging device. Therefore, typically, only a small fixed part of the network is observed during the entire experiment. However, in such an experiment, it can be hard to infer from the observed activity patterns whether (1) a neuron A directly affects neuron B, or (2) another, unobserved neuron C affects both A and B. To deal with this issue, we propose a “shotgun” observation scheme, in which, at each time point, we observe a small changing subset of the neurons from the network. Consequently, many fewer neurons remain completely unobserved during the entire experiment, enabling us to eventually distinguish between cases (1) and (2) given sufficiently long experiments. Since previous inference algorithms cannot efficiently handle so many missing observations, we develop a scalable algorithm for data acquired using the shotgun observation scheme, in which only a small fraction of the neurons are observed in each time bin. Using this kind of simulated data, we show the algorithm is able to quickly infer connectivity in spiking recurrent networks with thousands of neurons.