RT Journal Article SR Electronic T1 Proximodistal Structure of Theta Coordination in the Dorsal Hippocampus of Epileptic Rats JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 4760 OP 4775 DO 10.1523/JNEUROSCI.4297-14.2015 VO 35 IS 11 A1 Laurent, François A1 Brotons-Mas, Jorge R. A1 Cid, Elena A1 Lopez-Pigozzi, Diego A1 Valero, Manuel A1 Gal, Beatriz A1 de la Prida, Liset Menendez YR 2015 UL http://www.jneurosci.org/content/35/11/4760.abstract AB 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.