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Multipoint Optical DEvices for Minimally invasive neural circuits interface

Periodic Reporting for period 4 - MODEM (Multipoint Optical DEvices for Minimally invasive neural circuits interface)

Reporting period: 2021-04-01 to 2022-03-31

Among the neuroscience community there is widespread agreement that innovative research tools are required to better understand the incredible structural and functional complexity of the brain. To this aim, optical techniques based on genetically encoded neural activity indicators and actuators have represented a revolution for experimental neuroscience, allowing genetic targeting of specific classes of neurons and brain circuits. However, for optical approaches to reach their full potential, we need new generations of devices able to better interface with the extreme complexity and diversity of brain topology and connectivity.

MODEM has developed a set of innovative technologies for multipoint optical neural interfacing with the mammalian brain in vivo. These are approaches to based on modal multiplexing and de-multiplexing of light into a single, thin, minimally invasive tapered optical fiber serving as a carrier for multipoint signals to and from the brain. This has been achieved through nano- and micro-structuring of the taper edge, capitalizing on the photonic properties of the tapered waveguide to precisely control light delivery and collection in vivo.

The overall objectives achieved by the MODEM project are: 1) Development of minimally invasive technologies for versatile, user-defined optogenetic control over deep brain regions; 2) Development of fully integrated high signal-to- noise-ratio optrodes; 3) Development of minimally invasive technologies for multi-point in vivo all-optical “electrophysiology” through a single waveguide; 4) Development of new optical methodologies for dissecting brain circuitry at small and large scales.
The project MODEM focused on the main objective of developing a novel class of versatile multipoint optical/optoelectronic devices to serve as bidirectional neural interfaces. Mode division combined to advanced non-planar microfabrication was exploited to obtain neural implants Able to perform user-defined spatio-temporally triggered optogentic control neural activity over deep brain regions and subregions. This has allowed neuroscientists to deliver light into the brain with an improved matching between light emission geometries and the anatomy of brain region of interest. [Nature Neuroscience 20, 1180 (2017), Micro Electronic Engineering 195, 41 (2018), Scientific Reports 8, 4467 (2018)]. The ability to optically control neural activity with light pulses has been combined with the possibility to realize extracellular recording electrodes on the taper edge together with light emission points, resulting in a novel type of optoelectrical neural interfaces with reduced photoelectric artefacts [Peer reviewed article in press]. This is being exploited to study brain microcircuits with high spatial and temporal precision. The developed technology is not only able to bright light to the brain, but also to collect optical information from tissue. On this respect we implemented methods to collect fluorescence from sub-cortical structures with depth resolution [Nature Methods 16 1185 (2019); Optics Letters 14, 3856 (2020)], as well as fabrication methods to realize plasmonic structures on the edge of tapered fibers to implement vibrational spectroscopy or to modulate the incoming optical signal [Advanced Optical Materials 10, 2101649 (2022)]. The developed implantable techniques have been combined with optical and functional methods employed by neuroscientists to study neural networks, resulting in novel approaches to study brain causal connectivity at both local and brain-wide scales.
Modem has achieved several important progresses beyond the state of the art. (i) We have designed and fabrictaed devices able to tailor light delivery geometry with the anatomy of the brain region of interest, enabling neuroscientists to better target the sub-region of interest [Nature Neuroscience 20, 1180 (2017), Micro Electronic Engineering 195, 41 (2018), Scientific Reports 8, 4467 (2018)]. (ii) We have developed a method to optically monitor neural activity with depth resolution in sub-cortical structures, a feature unique to our technology [Nature Methods 16 1185 (2019), Biomedical Optics Express 12, 993 (2021), APL Photonics 7, 026106 (2022)] as well as pure mode-division demultiplexing. (iii) We have realized one of the first prototypes of plasmonic neural implants, e.g. implantable optical systems able to excite surface plasmon resonances on a system that can be implanted into the brain [Advanced Optical Materials 10, 2101649 (2022)]. (iv) We have developed several methods to pattern non-planar surfaces with non-constant radious of curvature, including focused ion beam milling of the taper edge on >100µm^2 and <50nm resolution [Advanced Optical Materials 10, 2101649 (2022)], focused ion beam deposition of extracellular recording electrodes [Peer reviewed paper accepted for publication], feedback-assisted multiphoton ablation of tapered waveguides [Optics Express 28 21368 (2020)] and non-planar two-photon photopolymerization electrodes [Peer reviewed article in press]. (v) We have implemented a method to identify the photometry efficiecny three-dimensional diagram of implanted systems by direct combination of light delivery and light collection fields [Frontiers in Neuroscience 13, 82 (2019)]. (vi) We have identified how the photometry efficiency field gets modified by the anatomy and optical properties of different brain structures [Biomedical Optics Express 12, 6081 (2021)].
Graphical representation of a tapered fiber collecting signal from multiple brain regions through mo