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Meeting Abstract

Next generation tracking microscopy for whole brain imaging of internal states


Li,  J
Research Group Systems Neuroscience & Neuroengineering, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Li, J. (2021). Next generation tracking microscopy for whole brain imaging of internal states. In 50th Annual Meeting of the Society for Neuroscience (Neuroscience 2021).

Cite as: https://hdl.handle.net/21.11116/0000-0009-86D7-D
Neuropsychiatric disorders, such as anxiety and depression, are network-wide disorders that affect multiple brain areas in frontolimbic and frontostriatal circuitries. Electrical stimulation has been hypothesized as a potential treatment for these conditions, but the optimal neural target and paradigm remain elusive. We posit that it’s critical to take a systems-level approach to interrogate neural activity in order to develop an understanding of neural dysfunction throughout relevant neural circuitry and intervention strategies. In these work, we record neural activity in multiple brain areas in a nonhuman primate (NHP) animal model and deliver electrical stimulation in prefrontal cortex. In order to demonstrate a functional link between mood state and neural state, we used a pharmacological approach to create a proxy for an acute anxiety animal model in the NHP model. Two NHP subjects were used in this study and experimental sessions were divided into three blocks. During the first block, baseline physiology and behavior was established. At the beginning of the second block, beta-carbolines, a type of benzodiazepine inverse agonist, were administered to induce an acute anxiety-like state. Finally, in the third block a treatment was administered to the subjects in the form of either closed-loop stimulation or midazolam, a known anxiolytic drug in the class of benzodiazepines. Using biomarkers of mood state changes discovered during this behavior, we designed closed-loop microstimulation protocols to mediate these changes and restore the subjects to a baseline, non-anxious state. We applied unilateral microstimulation to prefrontal cortical sites to modulate the response evoked from the beta-carbolines administered in the second block. We found that microstimulation was able to restore neural features across the neural circuitry to baseline levels and generate a profound anxiolytic physiological response.