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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.00586

Novel object recognition in rats with NMDAR dysfunction in CA1 after stereotactic injection of anti-NMDAR encephalitis cerebrospinal fluid

Maxi Kersten1, Theresa Rabbe1, Roman Blome1, Katrin Porath1, Tina Sellmann1, Christian G. Bien2,  Rüdiger Köhling1 and  Timo Kirschstein1*
  • 1University of Rostock, Germany
  • 2Epilepsy Center, Mara Hospital, Germany

Purpose: Limbic encephalitis associated with autoantibodies against N-methyl D-aspartate receptors (NMDARs) often presents with memory impairment. NMDARs are key targets for memory acquisition and retrieval, and have been mechanistically linked to its underlying process, synaptic plasticity. Clinically, memory deficits are largely compatible with a predominantly hippocampus-dependent phenotype, which, in rodents, is principally involved in spatial memory. Previous studies confirmed the impaired spatial memory in the rat model of anti-NMDAR encephalitis. Here, we hypothesized that nonspatial memory functions such as object recognition might also be affected in this model.
Methods: We performed stereotactic intrahippocampal bolus injection of human cerebrospinal fluid (CSF) from anti-NMDAR encephalitis and control patients into the hippocampus of the anesthetized rat. After recovery for 1-8 days, hippocampal slices were prepared from these animals and NMDAR-dependent long-term potentiation was assessed at the Schaffer collateral-CA1 synapse. In addition, we performed behavioral analyses using the open field and novel object recognition tasks.
Results: NMDAR-dependent long-term potentiation in the hippocampal CA1 area was significantly suppressed, indicating successful NMDAR dysfunction in this subfield. Spontaneous locomotor activity as well as anxiety-related behavior in the open field did not differ between NMDAR-CSF-treated and control animals. In the novel object recognition task, there were no differences in the motivation to approach objects. In contrast, we observed a significantly preferred exploration of the novel object only in control, but not in NMDAR-CSF-treated rats.
Conclusion: These results indicate that NMDAR dysfunction obtained by intrahippocampal stereotactic injection does not alter locomotor or anxiety-related behavior. In addition, approach to an object or exploratory behavior in general are not affected either, but intact initial NMDAR-dependent processes might be involved in novel object recognition.

Keywords: anti-NMDAR encephalitis, Cerebrospinal Fluid, Long-term potentation, object recognition, stereotactic injection

Received: 23 Dec 2018; Accepted: 17 May 2019.

Edited by:

Fernando Cendes, Campinas State University, Brazil

Reviewed by:

Roger Walz, Federal University of Santa Catarina, Brazil
Andre Schwambach Vieira, Campinas State University, Brazil  

Copyright: © 2019 Kersten, Rabbe, Blome, Porath, Sellmann, Bien, Köhling and Kirschstein. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Timo Kirschstein, University of Rostock, Rostock, 18057, Mecklenburg-Vorpommern, Germany, timo.kirschstein@uni-rostock.de