Roadmap on neurophotonics

Abstract

Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science’s grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain’s structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and ‘map’ them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken.

A Review of Intrinsic Optical Imaging Serial Blockface Histology (ICI-SBH) for Whole Rodent Brain Imaging

“…These tools were used to study, among other investigations, brain metabolism and neurodegenerative diseases [1,2]. Alongside these modalities, neurophotonics methods were developed to observe the brain with optical means, providing better spatial and temporal resolutions [3,4]. Light-tissue interaction mechanisms that can be used to study biological tissues include reflection, refraction, absorption, scattering, and some nonlinear optical effects such as two-photon excitation fluorescence (TPEF), second-and third-harmonic generation (SHG and THG, respectively), and Raman scattering [5].…”

Tapered Optical Fibers for Optogenetics: Ray Tracing Modeling

“…In µLEDs probes, light sources with a size ranging from tens µm 2 to hundreds µm 2 [11] are directly placed on implantable sapphire [12] or silicon shanks [13] or can be integrated on flexible implants with other components as temperature sensors or drug delivery channels [14,15] obtaining multifunctional devices. Due to their small dimension and low power consumption, µLEDs probes are convenient for freely-moving animal experiments, since no external light source is needed and support well wireless driving and powering [16,17,18]. Their main disadvantage, however, is represented by the heat induced by the LED driving current, which potentially adds up to light absorption in generating a temperature gradient beyond 2 °C [16,17,18].…”

“…Due to their small dimension and low power consumption, µLEDs probes are convenient for freely-moving animal experiments, since no external light source is needed and support well wireless driving and powering [16,17,18]. Their main disadvantage, however, is represented by the heat induced by the LED driving current, which potentially adds up to light absorption in generating a temperature gradient beyond 2 °C [16,17,18]. Flexible polymeric optical fibers [7,8,9], instead, exploit low stiffness to minimise tissue reaction over long-term implants.…”

Exploiting modal demultiplexing properties of tapered optical fibers for tailored optogenetic stimulation

“…This task is even more arduous when targeting brain regions beyond 1 mm depth, as common light-delivery methods (cleaved fiber optics and two-photon excitation) fail in penetrating such depths or are highly invasive. Driven by the experimental need for novel approaches, research in innovative technologies for deep brain light delivery has produced several promising solutions such as multi-dimensional wave-guides or highdensity µLED probes [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] . In a recent work 21 we demonstrated a simple and cost-effective device based on a thin Tapered Optical Fiber (TF) that can perform both homogeneous light delivery over large volumes and dynamically-controlled spatially-restricted illumination.…”