Opsin-free optical neuromodulation and electrophysiology enabled by a soft monolithic infrared multifunctional neural interface

Abstract

Controlling neuronal activity with high spatial resolution using multifunctional and minimally invasive neural interfaces constitutes an important step towards developments in neuroscience and novel treatments for brain diseases. While infrared neuromodulation is an emerging technology for controlling the neuronal circuitry, it lacks soft implantable monolithic interfaces capable of simultaneously delivering light and recording electrical signals from the brain while being mechanically brain-compatible. Here, we have developed a soft fibre-based device based on high-performance thermoplastics which are >100-fold softer than silica glass. The presented fibre-implant is capable of safely neuromodulating the brain activity in localized cortical domains by delivering infrared laser pulses in the 2 μm spectral region while recording electrophysiological signals. Action and local field potentials were recorded in vivo in adult rats while immunohistochemical analysis of the tissue indicated limited microglia and monocytes response introduced by the fibre and the infrared pulses. We expect our devices to further enhance infrared neuromodulation as a versatile approach for fundamental research and clinically translatable therapeutic interventions.

Mapping whole brain effects of infrared neural stimulation with positron emission tomography

“…This allowed us to temporally correlate the variation of the metabolic rate in all considered regions with the onset of the INS stimulus, thus excluding the possibility of the effects being caused by the implant and eliminating the need for sham experiments. The stimulation protocol, which was already validated by electrophysiological recordings in our previous study [32], was confirmed by the increase of the metabolic rate in the stimulated region. Global scale mapping of the glucose metabolism during the stimulation allowed to observe a rich network of connections in both the ipsi- and contralateral hemispheres.…”

“…In this study, we used soft infrared neural implants developed by our group for chronic INS applications described in [32] (Fig. 2A).…”

“…Electrophysiology is a well-konwn and technologically mature technique for studying neural activity with high sensitivity, temporal resolution and signal- to-noise ratio (SNR), and shares with INS the strength of not needing viral or chemical injections of ‘translators’ [30]. The combination of INS and electro-physiology in vivo in both acute and chronic experimental settings is further facilitated by the recent development of multifunctional implantable neural interfaces able to simultaneously deliver IR light in subcortical brain regions and record electrical signals [31, 32]. Because of all these factors, the combination of INS and PET is a powerful tool in neuroscience, allowing a broad range of complex in vivo experiments for the study of brain function in behaving animals on a scale ranging from the single axon to the whole brain.…”

Infrared neural stimulation and electrophysiology in a soft fiber-based neural interface

“…Commercially available rods of fluorinated ethylene-propylene (FEP) copolymer and polysulfone (PSU) were used as starting materials for the preform, [17][18][19] which was heated and pulled at a speed of 2 meters/minute to obtain a final fiber diameter of ∼ 400 μm (Figure 1a). Prior to the fiber fabrication, the viscosity-temperature profiles and refractive indices of both materials had been measured using a rotational rheometer (TA, Discovery Hybrid HR2) and ellipsometer (J.…”

“…All the procedures concerning the housing of rats, habituation in the animal facility, surgery and post-surgery care were approved by the national veterinary and food administration (permission number for the animal research: 2019-15-0201-00018) and in compliance with the European Union Directive 2010/63/EU. All details of the surgical procedures are described in Meneghetti et al 18…”