Our lab’s philosophy is to use the most suitable method(s) and animal model to answer experimental questions. For each experiment, our goal is to employ a combination of state-of- the-art methods such as, calcium imaging, optogenetics, and high-density electrophysiology to characterize the neural dynamics underlying haptics. We are strongly committed to building new methods that improve measurement and manipulation of brain activity. Tool building is largely accomplished through collaborative efforts with labs within the Rochester community and other higher-end institutions across the country. We aim for strong collaborations with other labs in the Brain & Cognitive Sciences department, which bolsters a strong program for signal processing and computational modeling.
Animal Models
Our ultimate goal is to understand how humans perceive and manipulate objects with our hands. To this end, we use animal models with hand dexterity that closely resembles that of humans. Non-human primates have refined sensory and motor hand skills, and neural representations that resemble those of humans. In addition to non- human primates, we also use transgenic mouse models to study genetically-tagged neural circuits using calcium imaging and optogenetics.
Electrophysiology & Genetic-Based Methods
for Imaging and Control of Neural Circuits
Our lab’s approach is to simultaneously record neural activity from many areas within the sensori-motor haptic network using high-density electrophysiology and neural imaging methods. We employ signal processing and computational modeling techniques to analyze the neural dynamics within and across recorded areas. Genetic-based optical tools such as optogenetics and calcium-based imaging (1-photon and 2- photon imaging) are powerful methods for characterizing neural circuits underlying behavior. These methods provide imaging and control of selective cell types (e.g., parvalbumin or pyramidal neurons), enabling us to study inhibitory and/or excitatory circuits with in vivo. While 2-photon microscopy provides superb spatial resolution of neural dynamics in different cell compartments (e.g., soma, and dendrites), improvements in viral transfection technology and optical techniques have made 1-photon microscopy a viable method for imaging individual cells, especially in large-scale mammalian brains. A powerful novel tool is the open-source UCLA miniscope device. In addition to using fluorescent molecules, our lab also uses chemogenetic approaches to study and control genetically-specific neural circuits. In particular, we use a novel chemogenetic method, developed by our collaborators, which leverages light from bioluminescent probes to drive optogenetic elements, and image calcium dynamics in vivo.
BioLuminescent-Optogenetics (BL-OG): This method replaces light from a fiber-optic cable with bioluminescent light generated within the cell itself. In BL-OG, bioluminescent luciferases are co-expressed with optogenetic elements, so that injection of a small molecule luciferin drives light production and regulates cellular activity.
Illustration of the BL-OG effect
Activity-dependent Bioluminescence: This method is used to monitor calcium dynamics in genetically-tagged cells without the use of an external light source. This is done by splitting the luciferase and uniting the two-halves with the calcium sensor, calmodulin-M13 (CaM-M13). This configuration leads to bioluminescence when calcium binds to the bioluminescent molecule and the luciferin is injected.