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Artifact-free Micro-LED Optoelectrode for Multi-color Neuromodulation

$556,525R01FY2025NSNIH

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

Abstract

Project Summary Significance: While exploration of brain mapping has been moving forward at an unprecedented scale and steady innovations in optogenetics have provided a toolset for identifying and manipulating of circuit components, still electrophysiology tools for monitoring and perturbing targeted neurons in multiple local circuits in the behaving animal are lagging. Understanding how local circuits perform in the brain requires high- density recording from a statistically representative fraction of neurons and targeted cell-specific perturbation of the circuit components. This grant application proposes to construct, test and disseminate micro-LED optoelectrode platforms that meet these requirements for analysis of dynamic activity of neural circuits at cellular resolution. Optogenetic stimulation gives effective means of high-accuracy circuit control with cell-type specificity. The proposed approach is to directly integrate micro-LEDs close to the recording sites on each probe shank. Neuron-sized lithographically-defined and monolithically-integrated LEDs allow scalable high- density stimulation. Various configurations of fiberless, multi-color, multi-shank, multi-sites optoelectrodes will be developed in a small form factor, comprising a micro-LED optoelectrode and driving/recording custom integrated circuit chips assembled in a single printed circuit board. By placing circuits close the optoelectrode probe, not only the noise can be significantly reduced but also the tethering can be simplified in a few wires, allowing artifact-free high-density scalability, light weight and compact form factor. Also, the custom driver chip can adjust the waveform for each individual micro LEDs, compensating possible variations in device characteristics for precise control of optical stimulation and reducing any induced artifacts. Preliminary Data: The previous work has demonstrated the feasibility of the optoelectrode that monolithically integrated lithographically-defined micro-LEDs onto the neural probes using GaN on silicon. Recording of light- induced neural activities has been observed with sub-microwatt illumination from each LED in the CA1 pyramidal cell layer. This selective local stimulation within very short distance enabled independent control of distinct neurons in the intact brain of freely moving mice. Specific Aims: In aim 1, high-density μLED optoelectrodes in different configurations for various animal models will be designed and optimized for artifact-free neural modulation at cellular level. In aim 2, novel hybrid integration technology will be applied to incorporate dual-color micro LEDs on the same shank at high density. In aim 3, validation of the proposed micro-LED probes will be carried out by precision timing of neuronal spikes for information processing in hippocampal circuitry.

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