Understanding the brain's inner workings requires studying the underlying complex networks that bind its basic computational elements, the neurons. Advances in extracellular neural recording techniques have enabled simultaneous recording of spike trains from multiple single neurons in awake, behaving subjects. Yet, devising methods to infer connectivity among these neurons has been significantly lacking. We introduce a connectivity inference framework based on graphical models. We first infer the functional connectivity between neurons by searching for clusters of statistically dependent spike trains. We then infer the effective connectivity between neurons within each cluster by building Dynamic Bayesian Network (DBN) model fit to the spike train data. Using probabilistic models of neuronal firing, we demonstrate the utility of this framework to infer neuronal connectivity in moderate and large scale networks with a substantial gain in performance compared to classical methods. We further use this framework to examine the role of spike timing correlation in infragranular layer V of the primary somatosensory cortex (S1) of the rat during unilateral whisker stimulation in vivo. Stable, whisker-specific networks provided more information about the stimulus than individual neurons' response. We finally demonstrate how this framework enables tracking and quantifying plastic changes in connectivity in biologically-plausible models of spike-timing-dependent-plasticity as well as changes in S1 response maps following sensory deprivation in the awake, behaving rat.
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