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We studied differences between optical and electrical micro-stimulation (MS) in the macaque frontal eye field (FEF) using single unit recordings, behavioral essay and fMRI. The frontal eye field serves as ideal test bed since it has been thoroughly characterized with electrical stimulation and because a behavioral effect (i.e. saccade) is easily induced by electrical MS. Three different constructs (AAV5-hSyn-eNpHR3.0, AAV5-hSyn-ChR2, AAV5-CAG-Arch) were injected to three FEF sites in two monkeys and robust firing rate modulations were observed upon light delivery. Although activity modulation was observed as far as 2mm away from the optical stimulation site, no significant voxel activation was found during combined fMRI and optical stimulation. High current electrical MS reliably induced saccades. Low current electrical MS combined with optical stimulation increased the probability of eliciting a saccade, suggesting optical stimulation may be similar to a low current electrical MS, known to induce an attentional bias. To test the possible effects of optical stimulation on attention monkeys were trained on a delayed memory saccade task. We observed significant changes in performance during optical stimulation trials, such as an increase in incorrect and missed trials, suggesting monkeys failed to perceive the instructed cue signal in the periphery.

A multitude of experiments over the past century have yielded deep insights into the cellular and synaptic organization of the microcircuitry of the neocortex and its possible role as a functional unit - a column of cells across 6 layers. The available data is, however, not standardized, is highly fragmented and often conflicting. More importantly, there are large gaps in our knowledge requiring an impractical number of experiments to fill. We therefore developed a strategy to accelerate a comprehensive analysis of the neocortical column by attempting to reconstruct it from partial information. We performed a spectrum of standardized biological experiments on strategic cellular and synaptic properties of the microcircuitry of the somatosensory cortex of a young rat and gathered further relevant data from previously published studies. We developed a generic supercomputer-based platform to build and simulate biologically-detailed brain models, and attempted to reconstruct a first draft of a unifying model at the cellular level of detail. The model integrates and unifies most of the current data, significantly predicts missing data, and provides a broad range of new insights into the structural and functional organization of neocortical microcircuitry. The model also serves as a virtual specimen for a new generation of simulation-based experimentation that can accelerate an integrated understanding of the cellular and synaptic basis of neocortical function.