With the continuing expansion of optogenetic tools, the central importance of optical measurement of neural activity has and will continue to grow. However, large scale optical approaches, such as pursued by the BRAIN Initiative, must overcome high light scattering in brain tissue. Moreover, optical approaches should be feasible in behaving animals, including freely moving mice. We will develop an ultra-miniature microendoscope, termed a needle optrode, made with a bare fiber bundle beveled to a fine tip. The smaller size and beveling improves tissue penetration and lowers tissue damage compared to existing technology, and arranges the field of view for imaging across layered structures such as neocortex. The core project contribution is achieving miniaturization through a lensless design, using an innovative coupling of array detector to enable fluorescence background rejection and remote focusing. We will demonstrate the power of our approach for collecting large scale, multiregion data by recording simultaneously from aligned cortical and thalamic regions of the mouse somatosensory system, in anesthetized mice. Completion of these aims will prepare us to record simultaneously throughout an entire thalamocortical whisker processing network, including both feedforward and feedback projections, and be a first step towards performing these recordings in an awake animal actively engaging objects of interest in a tactile task. Moreover, our approach --- providing multiregion, cellular resolution recording of genetically identified cell types, with possible extension to behaving animals --- will support similar experiments across brain regions and systems, as one of the high priority components of the BRAIN initiative.
We propose to develop a lensless microendoscope, called a needle optrode, that can be used for both in vivo imaging and optogenetic applications at arbitrary depths in brain tissue, and with significantly reduced tissue damage compared to existing techniques.
| Ba, C; Palmiere, M; Ritt, J et al. (2016) Dual-modality endomicroscopy with co-registered fluorescence and phase contrast. Biomed Opt Express 7:3403-3411 |
