title: Proximodistal structure of theta coordination in the dorsal hippocampus of epileptic rats.
abstract: Coherent neuronal activity in the hippocampal-entorhinal circuit is a critical mechanism for episodic memory function, which is typically impaired in temporal lobe epilepsy. To better understand how this mechanism is implemented and degraded in this condition, we used normal and epileptic rats to examine theta activity accompanying active exploration. Assisted by multisite recordings of local field potentials (LFPs) and layer-specific profiling of input pathways, we provide detailed quantification of the proximodistal coherence of theta activity in the dorsal hippocampus of these animals. Normal rats showed stronger coordination between the temporoammonic and perforant entorhinal inputs (measured from lamina-specific current source density signals) at proximal locations, i.e., closer to CA3; while epileptic rats exhibited stronger interactions at distal locations, i.e., closer to subiculum. This opposing trend in epileptic rats was associated with the reorganization of the temporoammonic and perforant pathways that accompany hippocampal sclerosis, the pathological hallmark of this disease. In addition to this connectivity constraint, we discovered that the appropriate timing between entorhinal inputs arriving over several theta cycles at the proximal and distal ends of the dorsal hippocampus was impaired in epileptic rats. Computational reconstruction of LFP signals predicted that restoring timing variability has a major impact on repairing theta coherence. This manipulation, when tested pharmacologically via systemic administration of group III mGluR antagonists, successfully re-established theta coordination of LFPs in epileptic rats. Thus, proximodistal organization of entorhinal inputs is instrumental in temporal lobe physiology and a candidate mechanism to study cognitive comorbidities of temporal lobe epilepsy.
authors: Instituto Cajal, CSIC, Madrid 28002, Spain and.
authors: François
authors: F
authors: Laurent
authors: Instituto Cajal, CSIC, Madrid 28002, Spain and.
authors: Jorge R
authors: JR
authors: Brotons-Mas
authors: Instituto Cajal, CSIC, Madrid 28002, Spain and.
authors: Elena
authors: E
authors: Cid
authors: Instituto Cajal, CSIC, Madrid 28002, Spain and.
authors: Diego
authors: D
authors: Lopez-Pigozzi
authors: Instituto Cajal, CSIC, Madrid 28002, Spain and.
authors: Manuel
authors: M
authors: Valero
authors: Instituto Cajal, CSIC, Madrid 28002, Spain and Universidad Europea de Madrid, Villaviciosa de Odón, Madrid 28670, Spain.
authors: Beatriz
authors: B
authors: Gal
authors: Instituto Cajal, CSIC, Madrid 28002, Spain and lmprida@cajal.csic.es.
authors: Liset Menendez
authors: http://orcid.org/0000-0002-0160-6472
authors: LM
authors: de la Prida
mesh_terms: D000818:Animals; D004827:Epilepsy / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013826:Theta Rhythm
keywords: coherence; multisite silicon probes; proximodistal; theta oscillations