A fundamental problem in neuroscience is to characterize the dynamics of spiking from the neurons in a circuit that is involved in learning about a stimulus or a contingency. A key limitation of current methods to analyze neural spiking data is the need to collapse neural activity over time or trials, which may cause the loss of information pertinent to understanding the function of a neuron or circuit. We introduce a new method that can determine not only the trial-to-trial dynamics that accompany the learning of a contingency by a neuron, but also the latency of this learning with respect to the onset of a conditioned stimulus. The backbone of the method is a separable two-dimensional (2D) random field (RF) model of neural spike rasters, in which the joint conditional intensity function of a neuron over time and trials depends on two latent Markovian state sequences that evolve separately but in parallel. Classical tools to estimate state-space models cannot be applied readily to our 2D separable RF model. We develop efficient statistical and computational tools to estimate the parameters of the separable 2D RF model. We apply these to data collected from neurons in the prefrontal cortex in an experiment designed to characterize the neural underpinnings of the associative learning of fear in mice. Overall, the separable 2D RF model provides a detailed, interpretable characterization of the dynamics of neural spiking that accompany the learning of a contingency.

Applied to binary response data from groups of individuals performing multi-day behavioral experiments, the model discriminates between-group differences and identifies subgroups.

We propose a general statistical framework for clustering multiple time series that exhibit nonlinear dynamics into an a-prioriunknown number of sub-groups. Our motivation comes from neuroscience, where an important problem is to identify, within a large assembly of neurons, subsets that respond similarly to a stimulus or contingency. Upon modeling the multiple time series as the output of a Dirichlet process mixture of nonlinear state-space models, we derive a Metropolis-within-Gibbs algorithm for full Bayesian inference that alternates between sampling cluster assignments and sampling parameter values that form the basis of the clustering. The Metropolis step employs recent innovations in particle-based methods. We apply the framework to clustering time series acquired from the prefrontal cortex of mice in an experiment designed to characterize the neural underpinnings of fear.