Technology develompent: whole-brain imaging, voltage imaging, optogenetics, computation
To study interactions between behavior, neurons and glia across the entire brain, we develop new technology for studying, analyzing and manipulating neural activity at the whole-brain scale. Here are examples of our tehnical work:
Function-guided brain-wide neural perturbation.
We combined whole-brain imaging with optogenetic perturbation and single-cell ablation. This technique allows for whole-brain functional mapping, followed by cell-resolution perturbation. Combined with computational analysis, it enables "on the fly hypothesis testing" -- measure activity everywhere; build a model; perturb brain activity to test the model.
Vladimirov et al., Nature Methods 2018
Distributed computation for analysis of large-scale data.
Whole-brain imaging generates large datasets, often hundreds of gigabytes per experiments. These datasets are hard to analyze on single workstations, and frequently require computer clusters. In this paper, we developed computational infrastructure for analyzing such datasets with distributed computation. Example analyses here include dimensionality reduction, whole-brain direction tuning, and others.
Freeman et al., Nature Methods 2016
Whole-brain imaging during virtual-reality behavior.
To perform whole-brain imaging in behaving zebrafish, we developed a system that combines light-sheet imaging with a virtual-reality system. Larval zebrafish can "swim around" in 2D virtual reality environments through a system that reads off their intended locomotion from electrical EEG activity from the tail motor nerves. A dual light-sheet microscope records whole-brain activity. We were very inspired by previous work in fruit flies rodents that similarly used VR environments to study neural activity in behaving animals.
Vladimirov et al., Nature Methods 2014
Whole-brain light-sheet imaging in zebrafish.
A "holy grail" in systems neuroscience has been to record from all neurons in the brain of a behaving animal. Here we did this using light-sheet imaging in zebrafish - an ideal combination of a technique and a suitable model organism: transparent, small, and genetically engineerable. Once you get whole-brain data, however, you realize what else you're missing! For example, calcium imaging is a slower and indirect readout of spiking. So we're not done yet!
Ahrens et al., Nature Methods 2013
Voltage imaging in zebrafish.
To get to spike-timing resolution, and image subthreshold voltage, we helped test voltage indicators in larval zebrafish. They work, currently in subpopulations of up to a few 100 cells. In the future we hope to scale this up to large brain volumes.
Abdelfattah et al., Science 2019