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Publication : Discrete subicular circuits control generalization of hippocampal seizures.

First Author  Fei F Year  2022
Journal  Nat Commun Volume  13
Issue  1 Pages  5010
PubMed ID  36008421 Mgi Jnum  J:327821
Mgi Id  MGI:7334297 Doi  10.1038/s41467-022-32742-x
Citation  Fei F, et al. (2022) Discrete subicular circuits control generalization of hippocampal seizures. Nat Commun 13(1):5010
abstractText  Epilepsy is considered a circuit-level dysfunction associated with imbalanced excitation-inhibition, it is therapeutically necessary to identify key brain regions and related circuits in epilepsy. The subiculum is an essential participant in epileptic seizures, but the circuit mechanism underlying its role remains largely elusive. Here we deconstruct the diversity of subicular circuits in a mouse model of epilepsy. We find that excitatory subicular pyramidal neurons heterogeneously control the generalization of hippocampal seizures by projecting to different downstream regions. Notably, anterior thalamus-projecting subicular neurons bidirectionally mediate seizures, while entorhinal cortex-projecting subicular neurons act oppositely in seizure modulation. These two subpopulations are structurally and functionally dissociable. An intrinsically enhanced hyperpolarization-activated current and robust bursting intensity in anterior thalamus-projecting neurons facilitate synaptic transmission, thus contributing to the generalization of hippocampal seizures. These results demonstrate that subicular circuits have diverse roles in epilepsy, suggesting the necessity to precisely target specific subicular circuits for effective treatment of epilepsy.
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