Light Scattering Properties Vary across Different Regions of the Adult Mouse Brain

Abstract

Recently developed optogenetic tools provide powerful approaches to optically excite or inhibit neural activity. In a typical in-vivo experiment, light is delivered to deep nuclei via an implanted optical fiber. Light intensity attenuates with increasing distance from the fiber tip, determining the volume of tissue in which optogenetic proteins can successfully be activated. However, whether and how this volume of effective light intensity varies as a function of brain region or wavelength has not been systematically studied. The goal of this study was to measure and compare how light scatters in different areas of the mouse brain. We delivered different wavelengths of light via optical fibers to acute slices of mouse brainstem, midbrain and forebrain tissue. We measured light intensity as a function of distance from the fiber tip, and used the data to model the spread of light in specific regions of the mouse brain. We found substantial differences in effective attenuation coefficients among different brain areas, which lead to substantial differences in light intensity demands for optogenetic experiments. The use of light of different wavelengths additionally changes how light illuminates a given brain area. We created a brain atlas of effective attenuation coefficients of the adult mouse brain, and integrated our data into an application that can be used to estimate light scattering as well as required light intensity for optogenetic manipulation within a given volume of tissue.

Genetically expressed voltage sensor ArcLight for imaging large scale cortical activity in the anesthetized and awake mouse

“…4). Based on the histological analysis and the limitations of blue light excitation, 44 we expect that the ArcLight response is predominantly from layer 2∕3 neurons (Fig. 1).…”

Noninvasive optical inhibition with a red-shifted microbial rhodopsin

“…Despite this better red light penetrance, however, myelination may still affect optical propagation in neural tissue and should therefore be taken into account given the experimental system in question 36,37 . The relative inexpensiveness and stability of red light sources may additionally be of use to experimental investigators, as well as the ability to avoid potentially confounding experimental visual artifacts, since mouse visual pigments peak at approximately 380 nm (ultraviolet cones) and 500 nm (green cones), but mouse vision above 600 nm is poor 38,39 .…”

Anterior Cingulate Cortex Input to the Claustrum Is Required for Top-Down Action Control

“…The light path angle (θ) was approximated to ensure accurate implantation, using the known refractive index ( n ) of cortical tissue (Sun et al, 2012) and the respective fiber NA according to the following formula: NA = n sinθ. The distance of light penetration for GCaMP6f detection and ChR2 activation was approximated using previous estimates for each technique (Cui et al, 2013; Al-Juboori et al, 2013). …”