Synaptic Remodeling of Entorhinal Input Contributes to an Aberrant Hippocampal Network in Temporal Lobe Epilepsy

Philipp Janz; Shakuntala Savanthrapadian; Ute Häussler; Antje Kilias; Sigrun Nestel; Oliver Kretz; Matthias Kirsch; Marlene Bartos; Ulrich Egert; Carola A Haas

doi:10.1093/cercor/bhw093

Synaptic Remodeling of Entorhinal Input Contributes to an Aberrant Hippocampal Network in Temporal Lobe Epilepsy

Standard

Synaptic Remodeling of Entorhinal Input Contributes to an Aberrant Hippocampal Network in Temporal Lobe Epilepsy. / Janz, Philipp; Savanthrapadian, Shakuntala; Häussler, Ute; Kilias, Antje; Nestel, Sigrun; Kretz, Oliver; Kirsch, Matthias; Bartos, Marlene; Egert, Ulrich; Haas, Carola A.

in: CEREB CORTEX, Jahrgang 27, Nr. 3, 01.03.2017, S. 2348-2364.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Janz, P, Savanthrapadian, S, Häussler, U, Kilias, A, Nestel, S, Kretz, O, Kirsch, M, Bartos, M, Egert, U & Haas, CA 2017, 'Synaptic Remodeling of Entorhinal Input Contributes to an Aberrant Hippocampal Network in Temporal Lobe Epilepsy', CEREB CORTEX, Jg. 27, Nr. 3, S. 2348-2364. https://doi.org/10.1093/cercor/bhw093

APA

Janz, P., Savanthrapadian, S., Häussler, U., Kilias, A., Nestel, S., Kretz, O., Kirsch, M., Bartos, M., Egert, U., & Haas, C. A. (2017). Synaptic Remodeling of Entorhinal Input Contributes to an Aberrant Hippocampal Network in Temporal Lobe Epilepsy. CEREB CORTEX, 27(3), 2348-2364. https://doi.org/10.1093/cercor/bhw093

Vancouver

Janz P, Savanthrapadian S, Häussler U, Kilias A, Nestel S, Kretz O et al. Synaptic Remodeling of Entorhinal Input Contributes to an Aberrant Hippocampal Network in Temporal Lobe Epilepsy. CEREB CORTEX. 2017 Mär 1;27(3):2348-2364. https://doi.org/10.1093/cercor/bhw093

Bibtex

@article{a5ead56231d44b2883155f9b526905b0,

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.",

keywords = "Animals, Dentate Gyrus, Disease Models, Animal, Entorhinal Cortex, Epilepsy, Temporal Lobe, Excitatory Postsynaptic Potentials, Green Fluorescent Proteins, Kainic Acid, Male, Mice, Inbred C57BL, Mice, Transgenic, Neural Pathways, Neuronal Plasticity, Synapses, Tissue Culture Techniques, Journal Article",

author = "Philipp Janz and Shakuntala Savanthrapadian and Ute H{\"a}ussler and Antje Kilias and Sigrun Nestel and Oliver Kretz and Matthias Kirsch and Marlene Bartos and Ulrich Egert and Haas, {Carola A}",

year = "2017",

month = mar,

day = "1",

doi = "10.1093/cercor/bhw093",

language = "English",

volume = "27",

pages = "2348--2364",

journal = "CEREB CORTEX",

issn = "1047-3211",

publisher = "Oxford University Press",

number = "3",

}

RIS

TY - JOUR

T1 - Synaptic Remodeling of Entorhinal Input Contributes to an Aberrant Hippocampal Network in Temporal Lobe Epilepsy

AU - Janz, Philipp

AU - Savanthrapadian, Shakuntala

AU - Häussler, Ute

AU - Kilias, Antje

AU - Nestel, Sigrun

AU - Kretz, Oliver

AU - Kirsch, Matthias

AU - Bartos, Marlene

AU - Egert, Ulrich

AU - Haas, Carola A

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

AB - 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.

KW - Animals

KW - Dentate Gyrus

KW - Disease Models, Animal

KW - Entorhinal Cortex

KW - Epilepsy, Temporal Lobe

KW - Excitatory Postsynaptic Potentials

KW - Green Fluorescent Proteins

KW - Kainic Acid

KW - Male

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Neural Pathways

KW - Neuronal Plasticity

KW - Synapses

KW - Tissue Culture Techniques

KW - Journal Article

U2 - 10.1093/cercor/bhw093

DO - 10.1093/cercor/bhw093

M3 - SCORING: Journal article

C2 - 27073230

VL - 27

SP - 2348

EP - 2364

JO - CEREB CORTEX

JF - CEREB CORTEX

SN - 1047-3211

IS - 3

ER -