Temporal lobe epilepsy (TLE) is one of the most common drug-resistant forms of epilepsy in adults and usually originates in the hippocampal formations. However, both the network mechanisms that support the seizure spread and the exact directions of ictal propagation remain largely unknown. Here we report the dissection of ictal propagation in the hippocampal–entorhinal cortex (HP–EC) structures using optogenetic methods in multiple brain regions of a kainic acid-induced model of TLE in VGAT-ChR2 transgenic mice. We perform highly temporally precise cross-area analyses of epileptic neuronal networks and find a feed-forward propagation pathway of ictal discharges from the dentate gyrus/hilus (DGH) to the medial entorhinal cortex, instead of a re-entrant loop. We also demonstrate that activating DGH GABAergic interneurons can significantly inhibit the spread of ictal seizures and largely rescue behavioural deficits in kainate-exposed animals. These findings may shed light on future therapeutic treatments of TLE.

Animal behavior usually has a hierarchical structure and dynamics. Therefore, to understand how the neural system coordinates with behaviors, neuroscientists need a quantitative description of the hierarchical dynamics of different behaviors. However, the recent end-to-end machine-learning-based methods for behavior analysis mostly focus on recognizing behavioral identities on a static timescale or based on limited observations. These approaches usually lose rich dynamic information on cross-scale behaviors. Here, inspired by the natural structure of animal behaviors, we address this challenge by proposing a parallel and multi-layered framework to learn the hierarchical dynamics and generate an objective metric to map the behavior into the feature space. In addition, we characterize the animal 3D kinematics with our low-cost and efficient multi-view 3D animal motion-capture system. Finally, we demonstrate that this framework can monitor spontaneous behavior and automatically identify the behavioral phenotypes of the transgenic animal disease model. The extensive experiment results suggest that our framework has a wide range of applications, including animal disease model phenotyping and the relationships modeling between the neural circuits and behavior.

Graphical Abstract AbstractRecent advances in optogenetics have established a precisely timed and cell-specific methodology for understanding the functions of brain circuits and the mechanisms underlying neuropsychiatric disorders. However, the fabrication of optrodes, a key functional element in optogenetics, remains a great challenge. Here, we report reliable and efficient fabrication strategies for chronically implantable optrode arrays. To improve the performance of the fabricated optrode arrays, surfaces of the recording sites were modified using optimized electrochemical processes. We have also demonstrated the feasibility of using the fabricated optrode arrays to detect seizures in multiple brain regions and inhibit ictal propagation in vivo. Furthermore, the results of the histology study imply that the electrodeposition of composite conducting polymers notably alleviated the inflammatory response and improved neuronal survival at the implant/neural-tissue interface. In summary, we provide reliable and efficient strategies for the fabrication and modification of customized optrode arrays that can fulfill the requirements of in vivo optogenetic applications.

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