We are currently working on a range of projects aimed at addressing and overcoming fundamental hurdles in modern neuroscience. This often involves open-source tool/technique development that is directly driven by specific, open questions in neuroscience. We then use these novel tools in lab and in collaboration with other groups to investigate neurological function within the context of complex behavior. Our research is open-source and highly collaborative and multi-disciplinary by nature.
Some research projects and areas of interest are outlined below
Long-term continuous neuro-behavioral recording and processing platforms for naturally behaving animals
A major challenge in neuroscience is to uncover how defined neural circuits in the brain encode, store, modify, and retrieve information. Adding to this challenge is the fact that neural function does not operate in isolation from but rather within living, behaving animals. To tackle this challenge, significant advancement of neural, behavioral, and computational tools is needed along with new experimental approaches to enable the detailed study of neural circuits within the context of complex behavior and natural, ethologically relevant environments.
We aim to solve these challenges by developing a neuro-behavioral recording platform using a new generation of Miniscopes that are powered remotely and transmit data wirelessly. The increased optical sensitivity of these Miniscopes will allow for uninterrupted, long-term imaging of neural activity across a field-of-view 5 times the larger than other miniature microscopes currently available. Animals will live in natural environments where an array of behavioral devices, integrated through a central DAQ, tracks animal position/pose, extracts complex behavioral “syllables”, monitors events in the environment, and provides an interface for behavioral tasks. A computational framework is being developed to process the large stream of data in real-time. Processed data will be shared, as it is collected, through an open-access, timeseries database for further analysis.
Long-term dynamics of CA1 pyramidal neurons
Using the above neuro-behavioral recording platform, we are working towards recording months-long, continuous neural activity across thousands of neurons while animals engage in complex behaviors across naturalistic environments. Data collected here will allow us and others to investigate neural activity at unprecedented scales and within the context of complex, unconstrained behavior. We believe this approach will shed light into the spaces between what traditional approaches have given us so far: producing lifelong “movies”, rather than individual “snapshots”, of neural dynamics and behavior across time, space, and task and allow us to ask “what does the lifetime of a place cell look like”.
Place cell dynamics across techniques and animal species
As neural imaging techniques in freely behaving animals advance, there are still open questions as to the source of place cell property differences across imaging and electrophysiological techniques in different animal species. Using an array of Miniscope and ephsy devices, we are working towards uncovering these differences and their sources.
Hippocampal dynamics during social interaction
SpatioTemporal Illumination Miniscope (STIMscope)
Additional new generations of minature microscopes
A full redesign of the Miniscope system, implementing all new optics, electronics, and software to address the approaching limitations inherent in current miniature microscopy platforms. This system extends the imaging capabilities of miniature microscopes to include larger fields-of-view (FOV), structured illumination, electrical focusing and FOV translation, multichannel excitation and detection, and native support for all previous Miniscope advancements. In addition, the system is being built as flexible hardware/software modules to allow for quick adaptation of future features.
Supported by the BRAIN Initiative and in collaboration with Dr. Michele Basso and Dr. Peyman Golshani, we are developing Miniscopes specifically for larger animal models such as rhesus macaque monkeys and marmosets. This project will generate longitudinal data sets of tens of thousands of neurons in monkeys performing freely behaving tasks. With the relaxed size and weight constrains that come with larger animal models, we are expanding the FOV to 30 times that of the standard Miniscope, incorporating all wireless data transmission, and adding microfluidic drug delivery channels. Within this project we are also developing deep brain optical implants and surgical protocols to support chronic multi-region imaging.
- Version 4 Miniscope
- Large FOV Miniscope for rats and larger animals
- Large FOV Miniscope for mice
- Dual excitation Miniscope for multi-channel imaging and single channel imaging plus optogenetic stimulation
- Electrophysiology integrated Miniscopes
- Wire-free Miniscopes
Integrating neural and behavior recording
- Miniscope DAQ Software
NSF NeuroNex Hub
Supported by our NSF NeuroNex Technology Hub, we are developing new Miniscopes that integrate electrophysiology recording in parallel with imaging. We currently are able to recording 32 electrode channels (with Tetrodes and/or Silicon probes) in conjunction with calcium imaging and are working on systems capable of reaching upwards of 192 electrode channels. As part of this project we are also designing a module capable of light-field microscopy and hardware for real-time processing of imaging data to drive optogenetic, electrical, and behavioral feedback.