Dense Packed Drivable Optrode Array for Precise Optical Stimulation and Neural Recording in Multiple-Brain Regions.

The input-output function of neural networks is complicated due to the huge number of neurons and synapses, and some high-density implantable electrophysiology recording tools with a plane structure have been developed for neural circuit studies in recent years. However, traditional plane probes are limited by the record-only function and inability to monitor multiple-brain regions simultaneously, and the complete cognition of neural networks still has a long way away. Herein, we develop a three-dimensional (3D) high-density drivable optrode array for multiple-brain recording and precise optical stimulation simultaneously. The optrode array contains four-layer probes with 1024 microelectrodes and two thinned optical fibers assembled into a 3D-printed drivable module. The recording performance of microelectrodes is optimized by electrochemical modification, and precise implantation depth control of drivable optrodes is verified in agar. Moreover, in vivo experiments indicate neural activities from CA1 and dentate gyrus regions are monitored, and a tracking of the neuron firing for 2 weeks is achieved. The suppression of neuron firing by blue light has been realized through high-density optrodes during optogenetics experiments. With the feature of large-scale recording, optoelectronic integration, and 3D assembly, the high-density drivable optrode array possesses an important value in the research of brain diseases and neural networks.

An artefact-resist optrode with internal shielding structure for low-noise neural modulation.

OBJECTIVE: The combination of optical manipulation of neural activities with electrophysiology recording is a promising technology for discovering mechanisms of brain disorders and mapping brain networks. However, fiber-based optrode is limited by the large size of light source and the winding of optical fiber, which hinders animal's natural movement. Meanwhile, the laser diode (LD)-based optrode restricted to the stimulation-locked artefacts will contaminate neural signal acquired from recording channels. APPROACH: Here, a reformative low-noise optrode with internal grounded shielding layer is proposed to mitigate the stimulus-locked artefacts generated during LDactivation for the application of optogenetics. MAIN RESULTS: The artefact mitigation capacity of grounded shielding was verified via simulation and experiments with transient amplitude of artefacts declined from over 5 mV to approximately 200 µV in-vitro. Meanwhile, the stimulation parameters were used based on previous studies by which neurons were activated without over heating the tissue as characterized by in-vitro studies (the output optical intensity is 823 ± 38 mW mm-2). Furthermore, the microelectrodes were modified with Poly (3, 4-ethylenedioxythiophene)-poly (styrenesulfonate) (PEDOT: PSS) to increase the signal recording quality of the optrode. Finally, in-vivo optogenetics experiments were carried in the hippocampus of one mouse and the results showed our low-noise optrode was qualified to achieve high-quality neural recording (signal-to-noise ratio about 13) and specific neuron stimulation simultaneously. SIGNIFICANCE: These results suggest the low-noise optrodes exhibit the ability of manipulating and recording neural dynamics and they are excellent candidates for neuroscience research.

Flexible and stretchable opto-electric neural interface for low-noise electrocorticogram recordings and neuromodulation in vivo.

Optogenetic-based neuromodulation tools is evolving for the basic neuroscience research in animals combining optical manipulation and electrophysiological recordings. However, current opto-electric integrated devices attaching on cerebral cortex for electrocorticogram (ECoG) still exist potential damage risks for both brain tissue and electrode, due to the mechanical mismatch and brain deformation. Here, we propose a stretchable opto-electric integrated neural interface by integrating serpentine-shaped electrodes and multisite micro-LEDs onto a hyperelastic substrate, as well as a serpentine-shaped metal shielding embedded in recording electrode for low-noise signal acquisition. The delicate structure design, ultrasoft encapsulation and independent fabrication followed by assembly are beneficial to the conformality, reliability and yield. In vitro accelerated deterioration and reciprocating tensile have demonstrated good performance and high stability. In vivo optogenetic activation of focal cortical areas of awaked mouse expressing Channelrhodopsin-2 is realized with simultaneous high-quality recording. We highlight the potential use of this multifunctional neural interface for neural applications.

The use of a double-layer platinum black-conducting polymer coating for improvement of neural recording and mitigation of photoelectric artifact.

The impedance of electrode and photostimulation artifacts (short-duration and high-amplitude spikes) are still hindering the employment of silicon-based neural probe in optogenetics. A fiber-based optrode modified with a double-layer platinum black-poly (3,4ethylenedioxythiophene) PEDOT/poly (4-styrenesulfonate) PSS (Pt-PP) coating has been developed for improvement of neural recording quality and mitigation of photoelectric artifact simultaneously. The Pt-PP coating was made by layer-by-layer electrochemical deposition followed by the ultrasonication and Cyclic Voltammetry (CV) scanning to verify its mechanical and electrochemical stability. Both in-vitro and in-vivo experiments demonstrated that Pt-PP coated optrode had outstanding recording performance (high signal-to-noise ratio about 9.64) and low photoelectric amplitude (850 µV). The artifact recovery time of Pt-PP coated optrode (0.3 ms) after photostimulation was significantly decreased when compared to platinum black (6 ms) or PEDOT/PSS (0.7 ms) coated one which has potential to retain high-quality neural signals in animal experiments. At last, the optogenetics experiments revealed the capability of Pt-PP coated optrode to record the change in neural spike rate with certain spatial resolution and shorter artifact recovery time. These results suggest that Pt-PP coating has great potential for neural electrodes in the application of neuroscience.

Active information maintenance in working memory by a sensory cortex.

Working memory is a critical brain function for maintaining and manipulating information over delay periods of seconds. It is debated whether delay-period neural activity in sensory regions is important for the active maintenance of information during the delay period. Here, we tackle this question by examining the anterior piriform cortex (APC), an olfactory sensory cortex, in head-fixed mice performing several olfactory working memory tasks. Active information maintenance is necessary in these tasks, especially in a dual-task paradigm in which mice are required to perform another distracting task while actively maintaining information during the delay period. Optogenetic suppression of neuronal activity in APC during the delay period impaired performance in all the tasks. Furthermore, electrophysiological recordings revealed that APC neuronal populations encoded odor information in the delay period even with an intervening distracting task. Thus, delay activity in APC is important for active information maintenance in olfactory working memory.

Flexible bioelectrodes with enhanced wrinkle microstructures for reliable electrochemical modification and neuromodulation in vivo.

Limited electrode size with high electrochemical performance and reliability of modified materials are two of the main concerns for flexible neural electrodes in recent years. Here, an effective fabrication method of enhanced micro-scale wrinkles based on oil-pretreated hyperelastic substrates (PDMS and Ecoflex) is proposed for the application of microelectrode biosensors. Compared to pre-stretching or compressing methods, this approach has better advantages including compatibility with MEMS processes on wafer and easy replication. Wrinkled gold microelectrodes exhibit superior electrochemical properties than the flat one, and no crack or delamination occurs after electroplating PEDOT:PSS and platinum black on wrinkled microelectrodes. Cyclic voltammetry (CV) scanning for 2500 times is performed to investigate adhesion and stability of modified materials. For the modified microelectrodes, no significant change is observed in charge storage capacity (CSC) and impedance at 1 kHz, whereas PEDOT:PSS coated flat microelectrodes appears delamination. Ultrasonication and cycling forces are also conducted on modified microelectrodes, which demonstrates little influence on the wrinkled ones. Flexible wrinkled microelectrodes are further verified by in-vivo ECoG recordings combined with optogenetics in mice. These results highlight the importance of micro-structure in neural electrode design and tremendous application potentials in flexible electronics.