Withoutrequiring repeatable trials, itcanflexibly capture covariate-dependent jointSCDs, andprovide interpretable latent causes underlying the statistical dependencies between neurons.

A promising way to extract computational principles from these large datasets is to train data-constrained recurrent neural networks (dRNNs).

Shared variability is separated into terms that express condition dependence, as well as trial-to-trial variation in trajectories.

The traditional approach to data-driven modeling of a neural population typically involves two separate stages. First, neural population activity is recorded while an animal performs a task of interest.

Closed-loop neuroscience experimentation, where recorded neural activity is used to modify the experiment on-the-fly, is critical for deducing causal connections and optimizing experimental time. Thus while new optical methods permit on-line recording (via Multi-photon calcium imaging) and stimulation (via holographic stimulation) of large neural populations, a critical barrier in creating closed-loop experiments that can target and modulate single neurons is the real-time inference of neural activity from streaming recordings. In particular, while multi-photon calcium imaging (CI) is crucial in monitoring neural populations, extracting a single neuron's activity from the fluorescence videos often requires batch processing of the video data. Without batch processing, dimmer neurons and events are harder to identify and unrecognized neurons can create false positives when computing the activity of known neurons. We solve these issues by adapting a recently proposed robust time-trace estimator---Sparse Emulation of Unused Dictionary Objects (SEUDO) algorithm---as a basis for a new on-line processing algorithm that simultaneously identifies neurons in the fluorescence video and infers their time traces in a way that is robust to as-yet unidentified neurons. To achieve real-time SEUDO (realSEUDO), we introduce a combination of new algorithmic improvements, a fast C-based implementation, and a new cell finding loop to enable realSEUDO to identify new cells on-the-fly with no warm-up period. We demonstrate comparable performance to offline algorithms (e.g., CNMF), and improved performance over the current on-line approach (OnACID) at speeds of 120 Hz on average. This speed is faster than the typical 30 Hz framerate, leaving critical computation time for the computation of feedback in a closed-loop setting.

Humans and animals are capable of flexibly switching between a multitude of tasks, each requiring rapid, sensory-informed decision making. Incoming stimuli are processed by a hierarchy of neural circuits consisting of millions of neurons with diverse feature selectivity. At any given moment, only a small subset of these carry task-relevant information. In principle, downstream processing stages could identify the relevant neurons through supervised learning, but this would require many example trials. Such extensive learning periods are inconsistent with the observed flexibility of humans or animals, who can adjust to changes in task parameters or structure almost immediately. Here, we propose a novel solution based on functionally-targeted stochastic modulation.

Recent advances in techniques for monitoring and perturbing neural populations have greatly enhanced our ability to study circuits in the brain. In particular, two-photon holographic optogenetics now enables precise photostimulation of experimenter-specified groups of individual neurons, while simultaneous two-photon calcium imaging enables the measurement of ongoing and induced activity across the neural population. Despite the enormous space of potential photostimulation patterns and the time-consuming nature of photostimulation experiments, very little algorithmic work has been done to determine the most effective photostimulation patterns for identifying the neural population dynamics. Here, we develop methods to efficiently select which neurons to stimulate such that the resulting neural responses will best inform a dynamical model of the neural population activity. Using neural population responses to photostimulation in mouse motor cortex, we demonstrate the efficacy of a low-rank linear dynamical systems model, and develop an active learning procedure which takes advantage of low-rank structure to determine informative photostimulation patterns. We demonstrate our approach on both real and synthetic data, obtaining in some cases as much as a two-fold reduction in the amount of data required to reach a given predictive power. Our active stimulation design method is based on a novel active learning procedure for low-rank regression, which may be of independent interest.

Latent Variable Models (LVMs) propose to model the dynamics of neural populations by capturing low-dimensional structures that represent features involved in neural activity. Recent LVMs are based on deep learning methodology where a deep neural network is trained to reconstruct the same neural activity given as input and as a result to build the latent representation. Without taking past or future activity into account such a task is non-causal. In contrast, the task of forecasting neural activity based on given input extends the reconstruction task. LVMs that are trained on such a task could potentially capture temporal causality constraints within its latent representation.