A Guide to Emerging Technologies for Large-Scale and Whole-Brain Optical Imaging of Neuronal Activity

Abstract

The mammalian brain is a densely interconnected network that consists of millions to billions of neurons. Decoding how information is represented and processed by this neural circuitry requires the ability to capture and manipulate the dynamics of large populations at high speed and resolution over a large area of the brain. While there has been a rapid increase in use of optical approaches in the neuroscience community over the last two decades, most microscopy approaches lack the ability to record the activity of all neurons comprising a functional network across the mammalian brain at relevant temporal and spatial resolution. In this review, we survey the recent development in the optical calcium imaging technologies in this regard and provide an overview of the strengths and limitations of each modality and their potential for scalability. We provide a guidance from a biological user perspective that is driven by the typical biological applications and sample conditions. We also discuss the potential for future advances and synergies that could be obtained through hybrid approaches or other modalities.

Cerebellar neurodynamics during motor planning predict decision timing and outcome on single-trial level

“…Our work expands on this observation by demonstrating the generality of the relevance on cerebellar neurodynamics in vertebrates and by quantitatively demonstrating how decision time and decision outcome could be decoded from this activity. Given current advances in large-scale, volumetric and high-speed calcium imaging (Ji et al, 2016;Yang and Yuste, 2017;Weisenburger and Vaziri, 2018), behavioral studies similar to ours can be expected to become possible in rodents, and to allow the activity of the entire cerebellum to be recorded. On a fundamental level, understanding how cerebellar activity is related to the timing and outcomes of action selection can provide insights into the functional role of the cerebellum during evolution, and the precise manner of its co-evolution with the cortex.…”

Bessel beam tomography for fast volume imaging

“…Imaging using extended beams, lines or light sheets offers a promising approach for increasing the imaging rate beyond point scanning methods [1][2][3][4]. Different from approaches that detect fluorescence using a camera, Bessel beam tomography uses non-descanned PMT detection.…”

“…To speed up volume imaging rates, extended volumes -instead of multiple focal spots -can be excited at the same time, for example using Bessel beams, line foci or light sheets. Combined with camera detectors, these approaches work best for weakly scattering samples [3,4], but Bessel beams or line foci [5] can also be used for imaging with non-descanned PMT detection. This is more suitable for imaging in scattering tissue and results in a projection of the entire imaging volume along the beam axis [8][9][10][11][12].…”

Capturing volumetric dynamics at high speed in the brain by confocal light field microscopy

“…Therefore, a number of faster imaging strategies have been introduced to meet this challenge, including new scanning mechanisms [2][3][4] , spatial and temporal multiplexing [5][6][7][8][9] and exploiting the sparsity of samples 2, 4, 10-12 . However, the fluorescence saturation and animals' tolerance of laser power still significantly limit the achievable imaging throughput [13][14][15][16] . Furthermore, capturing extremely fast dynamics, such as circulating blood cells, over an extended 3D volume has not yet been achieved.…”