Progress in neuroscience relies on new techniques for investigating the complex dynamics of neuronal networks. An ongoing challenge is to achieve minimally invasive and high-resolution observations of neuronal activity in vivo inside deep brain areas. Recently introduced methods for holographic control of light propagation in complex media enable the use of a hair-thin multimode optical fibre as an ultranarrow imaging tool. Compared to endoscopes based on graded-index lenses or fibre bundles, this new approach offers a footprint reduction exceeding an order of magnitude, combined with a significant enhancement in resolution. We designed a compact and high-speed system for fluorescent imaging at the tip of a fibre, achieving a resolution of 1.18 ± 0.04 µm across a 50-µm field of view, yielding 7-kilopixel images at a rate of 3.5 frames/s. Furthermore, we demonstrate in vivo observations of cell bodies and processes of inhibitory neurons within deep layers of the visual cortex and hippocampus of anaesthetised mice. This study paves the way for modern microscopy to be applied deep inside tissues of living animal models while exerting a minimal impact on their structural and functional properties.

Holographic optical tweezers (HOT) holds great promise for many applications in modern biophotonics, allowing the creation and measurement of minuscule forces on biomolecules, molecular motors and cells. Optical geometries used in HOT currently make use of bulk optics, and their usage in-vivo is compromised by the optically turbid nature of living tissues-a limiting factor in any advanced high-resolution imaging method. We present an alternative HOT approach in which multiple three-dimensional optical traps are introduced through a high-numerical-aperture multimode optical fibre, thus enabling an equally versatile means of optical manipulation through channels having cross-section comparable to the size of a single cell. Our work demonstrates real-time manipulation of 3-D arrangements of micro-objects, as well as the possibility of manipulating inside otherwise inaccessible cavities. We show that the position of the optical traps can be controlled with nanometric resolution over fibre lengths exceeding 100 mm. The results provide the basis for exploitation of holographic manipulation and other high-numerical-aperture techniques, including advanced forms of microscopy, through single-core-fibre endoscopes deep inside living tissues and other complex environments.

Digital micro-mirror devices (DMDs) have recently emerged as practical spatial light modulators (SLMs) for applications in photonics, primarily due to their modulation rates, which exceed by several orders of magnitude those of the already well-established nematic liquid crystal (LC)-based SLMs. This, however, comes at the expense of limited modulation depth and diffraction efficiency. Here we compare the beam-shaping fidelity of both technologies when applied to light control in complex environments, including an aberrated optical system, a highly scattering layer and a multimode optical fibre. We show that, despite their binary amplitude-only modulation, DMDs are capable of higher beam-shaping fidelity compared to LC-SLMs in all considered regimes.