Visualizing Seizure Propagation in Freely-moving Mice via Miniature Two-photon Microscopy
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06.21/
2023
Visualizing Seizure Propagation in Freely-moving Mice via Miniature Two-photon Microscopy
Zhuoran Zhang, Shihe Jiang, Kaibin Shi, Yan Li, Wei‑Na Jin, Qiang Liu, Ting Zhao, Heping Cheng, Fu‑Dong Shi
Publication: Neuroscience Bulletin
Read more: Visualizing Seizure Propagation in Freely-moving Mice via Miniature Two-photon Microscopy | Neuroscience Bulletin (springer.com)
Abstract
Due to the tight and precise associations between behaviors and neural activities, the investigation of neuronal activity in freely-moving and behaving animals is a major unaccomplished goal in neuroscience. Epileptiform seizures, characterized by hyper-synchronized discharges and hyper-excitation in neuronal networks, are one of the most common neurological disorders. However, the underlying mechanisms remain only partially understood. Characterizing the processes of their initiation and propagation is critical in understanding the pathophysiology of seizures. Over the past decade, advances in the development of in vivo Ca2+ imaging have accelerated insights into the modes and mechanisms underlying the neuronal discharges in seizures. Seizures are initiated by ensembles of proximal neuronal circuits which form the initiation site. Aberrant signals initiated here then propagate to neighboring areas via the preexisting neuronal connectome, while the ictal progression varies in time. Nevertheless, the prevailing knowledge of the course of seizure pathophysiology is derived from studies using ex vivo brain slices, anesthetized animals, or awake animals with a fixed head position. Studies on freely-moving unstrained animals are lacking.
We have recently assembled a fast high-resolution, miniaturized two-photon microscope (FHIRM-TPM), a platform capable of visualizing neuronal activity in freely-moving mice. This FHIRM-TPM system is equipped with a headpiece weighing 2.5 g mounted to the skull, allowing uninhibited movement with minimal stress and constraint. The FHIRM-TPM platform is capable of imaging cortical neurons as well as subcellular structures at the singlecell level with high spatiotemporal resolution. The same population of neurons exhibits different activation maps between freely-moving and head-fixed animals. Here, we multi-modally leveraged the FHIRM-TPM to illustrate the initiation and propagation of seizures in freely-moving mice with seizures induced by kainic acid injection, in conjunction with electroencephalography (EEG) recording and behavioral assessments.
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