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

Jongwoon Kim, Hengji Huang, Earl T. Gilbert, Kaiser C. Arndt, Daniel Fine English () and Xiaoting Jia ()
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Jongwoon Kim: Virginia Tech
Hengji Huang: Virginia Tech
Earl T. Gilbert: Virginia Tech
Kaiser C. Arndt: Virginia Tech
Daniel Fine English: Virginia Tech
Xiaoting Jia: Virginia Tech

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-46021-4

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