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Nat Neurosci. 2020 Jan 6. doi: 10.1038/s41593-019-0559-0. [Epub ahead of print]

Breakdown of spatial coding and interneuron synchronization in epileptic mice.

Author information

1
Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. tristan.shuman@mssm.edu.
2
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. tristan.shuman@mssm.edu.
3
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
4
Integrative Center for Learning and Memory, University of California, Los Angeles, Los Angeles, CA, USA.
5
Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
6
Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
7
Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology Hellas (FORTH), Heraklion, Greece.
8
School of Medicine, University of Crete, Heraklion, Greece.
9
Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
10
Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
11
Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology Hellas (FORTH), Heraklion, Greece. poirazi@imbb.forth.gr.
12
Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
13
Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
14
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. pgolshani@mednet.ucla.edu.
15
Integrative Center for Learning and Memory, University of California, Los Angeles, Los Angeles, CA, USA. pgolshani@mednet.ucla.edu.
16
Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. pgolshani@mednet.ucla.edu.
17
Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA. pgolshani@mednet.ucla.edu.
18
West LA Veterans Affairs Medical Center, Los Angeles, CA, USA. pgolshani@mednet.ucla.edu.
19
Intellectual and Developmental Disabilities Research Center, University of California, Los Angeles, Los Angeles, CA, USA. pgolshani@mednet.ucla.edu.

Abstract

Temporal lobe epilepsy causes severe cognitive deficits, but the circuit mechanisms remain unknown. Interneuron death and reorganization during epileptogenesis may disrupt the synchrony of hippocampal inhibition. To test this, we simultaneously recorded from the CA1 and dentate gyrus in pilocarpine-treated epileptic mice with silicon probes during head-fixed virtual navigation. We found desynchronized interneuron firing between the CA1 and dentate gyrus in epileptic mice. Since hippocampal interneurons control information processing, we tested whether CA1 spatial coding was altered in this desynchronized circuit, using a novel wire-free miniscope. We found that CA1 place cells in epileptic mice were unstable and completely remapped across a week. This spatial instability emerged around 6 weeks after status epilepticus, well after the onset of chronic seizures and interneuron death. Finally, CA1 network modeling showed that desynchronized inputs can impair the precision and stability of CA1 place cells. Together, these results demonstrate that temporally precise intrahippocampal communication is critical for spatial processing.

PMID:
31907437
DOI:
10.1038/s41593-019-0559-0

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