Report
Teaser, summary, work performed and final results
Periodic Reporting for period 2 - MODEM (Multipoint Optical DEvices for Minimally invasive neural circuits interface)
Teaser
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...
Summary
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 aspires to develop innovative technologies for multipoint optical neural interfacing with the mammalian brain in vivo. We are developing new approaches for 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 will be 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 of 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.
Work performed
We have developed minimally invasive probes to deliver light in deep brain regions with light emission patterns that can be customized depending on specific experimental needs. These consist of a tapered optical fiber with a tip having a diameter <1µm and length of a few millimeters. Tailoring the taper length and the refractive index of the waveguide it is possible to match the emission length of the implant with the depth of functional structures of the mouse brain like the cerebral cortex or the striatum [Nat Neuro 20 1180 (2017), Sci Rep 8 4467 (2018), IEEE ICTON 2018 10.1109/ICTON.2018.8473633]. For delivering light to multiple, dynamically selectable, portions of tissue, the taper is fully covered with metal and direct laser writing or focused ion beam milling are employed to remove the metal coating in specific portions of the device [Microelec Eng 195 14 (2018), Microelec Eng 192 88 (2018)]. This allows light to be emitted only where the metal is not present, therefore targeting specific sites of the brain. By exploiting the photonic properties of the taper and modulating the input angle of light it is possible to select the light delivery site, obtaining a dynamic addressing of the stimulation point.
Final results
The possibility to customize light delivery patterns depending on specific experimental needs is a unique feature of tapered optical fibers, and cannot be achieved with other technologies. This for instance allowed to develop a probe to control and monitor neural activity in the prefrontal cortex of the new born mice [Front in Neurosc 12 771 (2018)], taking advantage of the reduced invasiveness of the device. As an additional important feature, the fabrications methods based on direct laser writing and on focused ion beam allow structuring the taper around its entire surface, so to exploit the photonic properties of the narrowing waveguide.
The probes we are developing are indeed unique because the propagation constants of the guided lights are modified by the taper itself. This is a key feature to control light emission intensity at the different sections of the taper, in order to design a new generation of photonic implants.
The team is now working on the possibility to monitor neural activity by collecting functional fluorescent signals with tapered fibers in vivo [bioRxiv 455766 2018, Front in Neuroscience 13 82 2019] and by integrating electrodes for extracellular recording on the taper edge.