Unsupervised tracking and automated analysis of multi-population neural activity under anesthesia
Embargo Date
2023-05-23
OA Version
Citation
Abstract
Volatile anesthetics play an essential role in the practice of modern medicine due to their widespread use in general anesthesia. Research on anesthetics has mainly involved studies of molecular effects on ion channels and receptors, or on alterations of gross neural activity across large brain regions. We still lack an understanding of how these volatile anesthetics affect the neuronal network activity and bring about the anesthetized state at the mesoscale, composed of hundreds of identified excitatory and inhibitory neurons.
To address these issues, we developed a system that enables optical recording from multiple neuronal populations during extended, controlled states of anesthesia. We also built a pipeline that automates the processing of multisession datasets. By optimizing and using dual-color imaging, we recorded simultaneously the activity of excitatory neurons and subsets of inhibitory interneurons at different stages of anesthesia. The automated analysis pipeline allowed us to study the behavior of the same individual neurons across multiple states, which enabled us to determine the concentration-dependent effects isoflurane has on the excitatory and inhibitory populations in layer 2/3 of the primary somatosensory cortex. Although neuronal activity decreases at deeper levels of anesthesia, excitation and inhibition remain balanced when anesthetic concentrations are equilibrated. In contrast, the network reliably goes out of balance for several minutes when the level of anesthesia is changed. Correlations in activity of neighboring neurons increased globally during anesthesia, while the local spatial gradients in correlation were remarkably independent of the anesthetic state.
By studying the effects of volatile anesthetics at the level of cortical microcircuits, we have developed a better understanding of these effects on neuronal populations and consequently how the state of anesthesia is produced. This understanding can help improve medical practice for populations susceptible to debilitating effects due to anesthetic exposure, specifically infants that can suffer from developmental problems and the elderly that can develop post-operative delirium and cognitive impairment. For a broader range of patients, our results suggest that anesthetization protocols should be designed to keep the patient in a quasi-steady-state of anesthetization, with as few transitions as is practical.
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License
Attribution-ShareAlike 4.0 International