title: Synaptic Remodeling of Entorhinal Input Contributes to an Aberrant Hippocampal Network in Temporal Lobe Epilepsy.
abstract: The hippocampus is reciprocally connected with the entorhinal cortex. Although several studies emphasized a role for the entorhinal cortex in mesial temporal lobe epilepsy (MTLE), it remains uncertain whether its synaptic connections with the hippocampus are altered. To address this question, we traced hippocampo-entorhinal and entorhino-hippocampal projections, assessed their connectivity with the respective target cells and examined functional alterations in a mouse model for MTLE. We show that hippocampal afferents to the dorsal entorhinal cortex are lost in the epileptic hippocampus. Conversely, entorhino-dentate projections via the medial perforant path (MPP) are preserved, but appear substantially altered on the synaptic level. Confocal imaging and 3D-reconstruction revealed that new putative contacts are established between MPP fibers and dentate granule cells (DGCs). Immunohistochemical identification of pre- and postsynaptic elements indicated that these contacts are functionally mature synapses. On the ultrastructural level, pre- and postsynaptic compartments of MPP synapses were strongly enlarged. The length and complexity of postsynaptic densities were also increased pointing to long-term potentiation-related morphogenesis. Finally, whole-cell recordings of DGCs revealed an enhancement of evoked excitatory postsynaptic currents. In conclusion, the synaptic rearrangement of excitatory inputs to DGCs from the medial entorhinal cortex may contribute to the epileptogenic circuitry in MTLE.
authors.affiliation: Experimental Epilepsy Research, Department of Neurosurgery.|Faculty of Biology.
authors.forename: Philipp
authors.initials: P
authors.lastname: Janz
authors.affiliation: Faculty of Biology.|Institute for Physiology I, Systemic and Cellular Neurophysiology.
authors.forename: Shakuntala
authors.initials: S
authors.lastname: Savanthrapadian
authors.affiliation: Experimental Epilepsy Research, Department of Neurosurgery.
authors.forename: Ute
authors.initials: U
authors.lastname: Häussler
authors.affiliation: Faculty of Biology.|Laboratory for Biomicrotechnology, Department of Microsystems Engineering, Freiburg im Breisgau 79110, Germany.|Bernstein Center Freiburg, Freiburg im Breisgau 79104, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Kilias
authors.affiliation: Neuroanatomy, Department of Anatomy and Cell Biology.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Nestel
authors.affiliation: Renal Division, Department of Medicine, University Medical Center Freiburg, Freiburg im Breisgau 79106, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kretz
authors.affiliation: Neuroanatomy, Department of Anatomy and Cell Biology.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kirsch
authors.affiliation: Institute for Physiology I, Systemic and Cellular Neurophysiology.|Bernstein Center Freiburg, Freiburg im Breisgau 79104, Germany.|BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Freiburg im Breisgau 79110, Germany.
authors.forename: Marlene
authors.initials: M
authors.lastname: Bartos
authors.affiliation: Laboratory for Biomicrotechnology, Department of Microsystems Engineering, Freiburg im Breisgau 79110, Germany.|Bernstein Center Freiburg, Freiburg im Breisgau 79104, Germany.|BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Freiburg im Breisgau 79110, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Egert
authors.affiliation: Experimental Epilepsy Research, Department of Neurosurgery.|Bernstein Center Freiburg, Freiburg im Breisgau 79104, Germany.|BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Freiburg im Breisgau 79110, Germany.
authors.forename: Carola A
authors.initials: CA
authors.lastname: Haas
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000473:pathology* / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000473:pathology* / Q000503:physiopathology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007608:Kainic Acid; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology; D013569:Synapses / Q000473:pathology* / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D007608:Kainic Acid
keywords: granule cells; kainate; perforant path; spines; synaptic plasticity