Predicting synchronous firing of large neural populations from sequential recordings

A major goal in neuroscience is to understand how populations of neurons code for stimuli or actions. While the number of neurons that can be recorded simultaneously is increasing at a fast pace, in most cases these recordings cannot access a complete population: some neurons that carry relevant information remain unrecorded. In particular, it is hard to simultaneously record all the neurons of the same type in a given area. Recent progress have made possible to profile each recorded neuron in a given area thanks to genetic and physiological tools, and to pool together recordings from neurons of the same type across different experimental sessions. However, it is unclear how to infer the activity of a full population of neurons of the same type from these sequential recordings. Neural networks exhibit collective behaviour, e.g. noise correlations and synchronous activity, that are not directly captured by a conditionally-independent model that would just put together the spike trains from sequential recordings. Here we show that we can infer the activity of a full population of retina ganglion cells from sequential recordings, using a novel method based on copula distributions and maximum entropy modeling. From just the spiking response of each ganglion cell to a repeated stimulus, and a few pairwise recordings, we could predict the noise correlations using copulas, and then the full activity of a large population of ganglion cells of the same type using maximum entropy modeling. Remarkably, we could generalize to predict the population responses to different stimuli with similar light conditions and even to different experiments. We could therefore use our method to construct a very large population merging cells’ responses from different experiments. We predicted that synchronous activity in ganglion cell populations saturates only for patches larger than 1.5mm in radius, beyond what is today experimentally accessible.Author summary: A major goal of neuroscience is to understand how entire populations of neurons process sensory stimuli. This understanding is limited because current experimental techniques do not allow to record all relevant neurons of a sensory structure. A possible strategy to overcome this issue, is to use sequential recordings from cells recorded in multiple experiments to reconstruct how the entire population will respond. Yet this approach can not account for collective behaviour and synchronous activity within the population. Here we address this issue in the retina and propose a method to infer the activity of an entire population of neurons of the same type from sequential recordings. Our method assumes that we have access to many single cell recordings gathered from different experiments, and additionally to a few synchronous recordings of pairs of neurons of the same type. By combining copula distributions and maximum entropy modeling, we used these data to reconstruct the collective activity of a large population of neurons and to show how synchrony grows with the number of neurons.