Breakdown of spatial coding and interneuron synchronization in epileptic mice

Abstract

Temporal lobe epilepsy causes severe cognitive deficits, but the circuit mechanisms remain unknown. Interneuron death and reorganization during epileptogenesis may disrupt the synchrony of hippocampal inhibition. To test this, we simultaneously recorded from the CA1 and dentate gyrus in pilocarpine-treated epileptic mice with silicon probes during head-fixed virtual navigation. We found desynchronized interneuron firing between the CA1 and dentate gyrus in epileptic mice. Since hippocampal interneurons control information processing, we tested whether CA1 spatial coding was altered in this desynchronized circuit, using a novel wire-free miniscope. We found that CA1 place cells in epileptic mice were unstable and completely remapped across a week. This spatial instability emerged around 6 weeks after status epilepticus, well after the onset of chronic seizures and interneuron death. Finally, CA1 network modeling showed that desynchronized inputs can impair the precision and stability of CA1 place cells. Together, these results demonstrate that temporally precise intrahippocampal communication is critical for spatial processing. David Geffen School of Medicine Dean's Fund for development of open-source miniaturized microscopes to B.

Extended field-of-view ultrathin microendoscopes for high-resolution two-photon imaging with minimal invasiveness in awake mice

“…We reported the spatial map of encoding of such information in the VPM nucleus, maintaining unaltered the bidirectional cortico-thalamic connectivity. GRIN lenses, alone or in combination with fiber-bundles, have been used to perform one-and twophoton endoscopic imaging in deep brain areas, such as the hippocampus [50][51][52] , the striatum 27 , and the hypothalamus 27,53,54 . GRIN microendoscopes have also been used to perform simultaneous functional imaging of two different brain regions 55 , allowing concurrent monitoring of neuronal dynamics in areas otherwise not accessible with single FOV systems.…”

The McGill-Mouse-Marmoset Platform: A Standardized Approach for High-throughput Imaging of Neuronal Dynamics During Behavior

“…However, recent initiatives in open source development of miniscopes pave the way for a multitude of independently designed and modified miniscopes in the near future, with a variety of unique uses 33 . These include integration with optogenetic manipulations 34 and wire-free miniscopes for efficient monitoring of social behaviour 35 . The miniaturization of two-photon microscopy introduces optical sectioning for three-dimensional imaging and improved spatial resolution of cells, which permits tracking of cellular processes at the scale of individual dendritic spines during behavior, while altogether minimizing widespread photobleaching from single-photon imaging 36 .…”

Disrupted Spatial Maps in Epilepsy Highlight the Importance of Timing in Neural Codes

“…A tour de force, employing highdensity electrophysiology, chronic wireless one-photon calcium imaging in freely moving animals, electroencephalogram, computational modeling, and behavior, their study confirms several observations from other laboratories, adds unprecedented time line data about the evolution of functional disruption during disease progression, and puts forth an "input timing" hypothesis for memory deficits. 1 Neurons within the rodent hippocampus have tuning curves that reflect the spatial position of the animal, so called "place cells." Place cells are thus active when animals are at specific locations in a maze.…”