Cortical neurons represent sensory and motor features. What circuit mechanisms shape cortical coding? Which neurons drive behavior? Our lab addresses these questions using optical approaches in head fixed mice.
By combining carefully designed behavioral assays with advanced optical techniques, we hope to determine the minimal subset of neurons whose perturbation can impact behavior.
In sensory cortex, neurons with common tuning are more interconnected than neurons with distinct tuning. We are probing how such connectivity enables computations like amplification, pattern completion, and feature detection.
Our experiments depend on rapid turnaround of terabyte-scale datasets. We are developing pipelines to process data acquired during calcium imaging and behavioral videography, and to relate neural activity to behavior.
Approaches such as high speed videography and image processing allow precise measurements of the behavioral state of the animal. Tasks are designed so that even subtle changes in the animal's behavior can be detected.
Two-photon microscopy using modern calcium indicators allows us to record the activity of thousands of cortical neurons during behavior. Neurons can be tracked over months, and structural indicators can label cell types.
A prerequisite to exploring the behavioral roles of neurons is understanding the spatial distribution of functional neural types. We are actively generating mesoscale maps of cortex during behavior, on the 10K-100K neuron scale.
Neurons encoding particular features are typically intermingled with other neurons from which they are genetically inseparable. Approaches like multiphoton ablation and two-photon optogenetics allow for lesioning and activation with cellular precision, making it possible to target intermingled populations.
Peron SP, Chen TW, Svoboda K
2015, Curr. Opinion Neurobiology
Peron SP, Freeman J, Iyer V, Guo C, Svoboda K
Huber D, Gutnisky DA, Peron SP, O'Connor DH, Wiegert JS, Tian L, Oertner TG, Looger LL, Svoboda K
Peron SP, Svoboda K
2011, Nature Methods (outlook)
O'Connor DH, Peron SP, Huber D, Svoboda K
Simon earned his PhD with Fabrizio Gabbiani at Baylor College of Medicine, studying single neuron computation in the context of insect vision. He did his postdoctoral work with Karel Svoboda at Janelia Farm, working on mechanisms of cortical processing in the behaving mouse using two-photon microscopy.
Dan earned his PhD with Richard Salvi at SUNY Buffalo, focusing on the mechanisms of tinnitus. He did postdoctoral work with Stephen Lomber at U. Western Ontario.
Klavdia earned her undergraduate degree in mathematics from Caltech, and a masters degree in economics from Northwestern.
Canonical experiments from the laboratories of Bill Newsome and Ranulfo Romo demonstrated that perturbing small groups of sensory cortical neurons can influence perception. Modern optical techniques open the door to performing cellular resolution loss- and gain-of-function experiments, potentially allowing the field to understand how individual neurons, and not just small patches of cortex, influence perception. We are using a combination of naturalistic and synthetic perception paradigms, in conjunction with multiphoton ablation and two-photon optogenetics, to probe the way in which small groups of neurons impact animal choice and, ultimately, perception.
The famed Canadian neuropsychologist Donald Hebb long ago proposed that neurons that fire together wire together. Recent work has shown that sensory cortical neurons are indeed wired in such a homotypic manner -- that is, neurons with similar sensory tuning are interconnected far more than other neurons. What is the computational function of these enhanced connections? How do they shape neural activity? Are there other mechanisms that contribute to the enhanced feature selectivity these connections are believed to drive? We use two preparations to ask these question: mice performing a vibrissal object-localization task, and mice performing a synthetic perception task where the stimulus is exclusively optogenetic.