Optimization of Clear Optically Matched Panoramic Access Channel Technique (COMPACT)
for large-scale deep-brain neurophotonic interface
With the advance of sensitive molecular indicators and actuators, neurophotonics has become a powerful
paradigm for discovering the principles underlying neural circuit functions. However, a major obstacle of
using light to study neurons located deep in the mammalian brain is the limited access depth. Even with the
advance of multiphoton microscopy, the majority of implementation for imaging the mammalian brain is
limited to ~ 1 mm in depth. The majority of the mouse brain still remains inaccessible to cellular resolution
measurement, not to mention the brain of larger mammals. To image deep brain regions, invasive miniature
optical probes are required. One key issue with these optical probes is the tiny tissue access volume which
limits the number of neurons to be imaged and reduces the success rate of experiments.
Towards large-scale deep-brain neurophotonic interface, we have recently developed Clear
Optically Matched Panoramic Access Channel Technique (COMPACT), which can effectively increase the
tissue access volume by ~ three orders of magnitude. To maximize the impact of the COMPACT platform,
we propose to optimize COMPACT in three major areas. First, we will further miniaturize the implementation
of COMPACT. Second, we will enable COMPACT based fiber photometry and optogenetics. For these two
applications, we can further reduce the capillary diameter to 160 µm. Multiple capillaries can be inserted in
the mammalian brain to create the neurophotonic interface “highway” system. This development will
complement the existing paradigm of mesoscale sampling with electrode array probes by providing an
optical version of whole-brain-access high-capacity recording and modulation system. Third, we will develop
head-mounted two-photon COMPACT system for freely moving animal studies.
To benchmark the system performance, we will carry out extensive in vivo measurement of neuronal
structure and activity in the living mouse brain. Specifically, we will quantify and optimize the imaging
resolution, signal-to-noise ratio, and maximum imaging depth outside capillary. Moreover, we will simplify
and automate the operation procedure so that it can be easily adopted by neurobiologists. With the
progress of the technology development, we will also work to broadly disseminate the COMPACT based
technologies. In addition to scientific publication, we will develop a comprehensive website similar to that of
the Miniscope project to include the detailed mechanical and optical design files, system calibration and
alignment routines, surgical procedures, and customized control software. The ultimate goal is to make
COMPACT robust, turn-key, and broadly available to transform how we use light to study mammalian brains.
