T-DOpE probes reveal sensitivity of hippocampal oscillations to cannabinoids in behaving mice

• Published in: Nature communications Vol. 15; no. 1; p. 1686
• Main Authors: Kim, Jongwoon, Huang, Hengji, Gilbert, Earl T., Arndt, Kaiser C., English, Daniel Fine, Jia, Xiaoting
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.02.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/62; 631/1647/1453/2205; 631/1647/2253; 631/378/1595/1554; 64/60; 9/30; Action Potentials - physiology; Agonists; Animals; Automation; Cannabinoid CB1 receptors; Cannabinoids - pharmacology; Down-regulation; Drug delivery; Electrophysiological recording; Electrophysiology; Fabrication; Firing pattern; Genetic engineering; Genetics; Hippocampus; Hippocampus - physiology; Humanities and Social Sciences; Information processing; Memory; Mice; Microfluidics; multidisciplinary; Neuromodulation; Neurons; Neurons - physiology; Neurosciences; Optical waveguides; Optics; Oscillations; Probes; Ripples; Science; Science (multidisciplinary); Stimulation; Tapering; Theta rhythms; Ultrafines
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-46021-4

Understanding the neural basis of behavior requires monitoring and manipulating combinations of physiological elements and their interactions in behaving animals. We developed a thermal tapering process enabling fabrication of low-cost, flexible probes combining ultrafine features: dense electrodes, optical waveguides, and microfluidic channels. Furthermore, we developed a semi-automated backend connection allowing scalable assembly. We demonstrate T-DOpE (Tapered Drug delivery, Optical stimulation, and Electrophysiology) probes achieve in single neuron-scale devices (1) high-fidelity electrophysiological recording (2) focal drug delivery and (3) optical stimulation. The device tip can be miniaturized (as small as 50 µm) to minimize tissue damage while the ~20 times larger backend allows for industrial-scale connectorization. T-DOpE probes implanted in mouse hippocampus revealed canonical neuronal activity at the level of local field potentials (LFP) and neural spiking. Taking advantage of the triple-functionality of these probes, we monitored LFP while manipulating cannabinoid receptors (CB1R; microfluidic agonist delivery) and CA1 neuronal activity (optogenetics). Focal infusion of CB1R agonist downregulated theta and sharp wave-ripple oscillations (SPW-Rs). Furthermore, we found that CB1R activation reduces sharp wave-ripples by impairing the innate SPW-R-generating ability of the CA1 circuit. Neural activity is regulated by synapse-neuromodulator interactions, necessitating optoelectro-pharmacological investigations. Here, authors implement their multi-modal probe to show focal infusion of synthetic cannabinoid disrupts CA1 oscillations.