Brain functions rely on the coordinated dynamics of a vast number of highly interconnected neurons. To discern how these dynamics lead to behavior, Vaziri seeks to capture neuronal activity over large brain volumes at high speed and single-cell resolution across species. His lab develops and uses imaging techniques addressing these demands to generate functional maps of neuronal circuits up to the level of a whole brain in behaving animals.
To fully understand how sensory input leads to behavior, it is necessary to not only map connections between neurons, but also examine how these cells interact in real time and how their collective dynamics influence behavior. To do so, new tools are required to excite neurons in specific spatiotemporal patterns, while capturing their activity across entire functional networks on a physiologically relevant timescale and at single-cell resolution.
Vaziri develops new high-speed functional optical techniques that meet this challenge. With these tools, he seeks to uncover the biological mechanisms and ultimately the computational and theoretical principles by which sensory inputs are represented and interact with internal states to generate behavior.
One of these tools, light sculpting, uses temporal focusing to disperse the spectrum of femtosecond laser pulses, which are then brought back into register, generating a wide-field two-photon excitation that is axially highly confined. Three-dimensional data can be obtained by scanning the wide-field two-photon in the axial direction. Using genetically encodable calcium sensors, the lab has developed a microscope that can capture brain-wide dynamics in C. elegans at high speed.
Applying a variation of this approach to neurons engineered to express light-sensitive channel rhodopsin, Vaziri and his colleagues have also shown that individual cells can be selectively activated at high speed. Variations on this technique have made it possible to mimic the excitation patterns target neurons would receive from the environment.
Another technique developed by Vaziri and his collaborators makes it possible to record signals on even greater scales and at higher speeds than has been possible previously. Light-field deconvolution microscopy employs an array of microlenses to simultaneously capture views from a large number of angles, without any moving components. These views are then recombined to generate a three-dimensional representation. This technique has made it possible to capture the activity of thousands of neurons across the entire brain of the larval zebrafish, which the lab uses as a model to understand the emergence of high-level feature recognition and action selection.
The Vaziri lab continues to refine these and other techniques, and extend their use across species. One of the main frontiers in the field is the creation of tools to capture the functional dynamics of large-scale neuronal circuits in awake, behaving rodents. Working toward this goal Vaziri’s lab has recently demonstrated an unbiased high-speed calcium imaging technique based on light sculpting that has made it possible to capture the majority of a mouse cortical column at single-cell resolution.
Ultimately, Vaziri hopes to examine the computation algorithms with which the brain performs various tasks. In addition, his lab is broadly involved in using other optical tools, such as single-molecule techniques, and exploring new ways of applying quantum optics to other biological questions.