Quinolinic acid injection in mouse medial prefrontal cortex affects reversal learning abilities, cortical connectivity and hippocampal synaptic plasticity

Amira Latif-Hernandez, Disha Shah, Tariq Ahmed, Adrian C. Lo, Zsuzsanna Callaerts-Vegh, Annemie Van Der Linden, Detlef Balschun, Rudi D'Hooge

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Intracerebral injection of the excitotoxic, endogenous tryptophan metabolite, quinolinic acid (QA), constitutes a chemical model of neurodegenerative brain disease. Complementary techniques were combined to examine the consequences of QA injection into medial prefrontal cortex (mPFC) of C57BL6 mice. In accordance with the NMDAR-mediated synapto- and neurotoxic action of QA, we found an initial increase in excitability and an augmentation of hippocampal long-term potentiation, converting within two weeks into a reduction and impairment, respectively, of these processes. QA-induced mPFC excitotoxicity impaired behavioral flexibility in a reversal variant of the hidden-platform Morris water maze (MWM), whereas regular, extended MWM training was unaffected. QA-induced mPFC damage specifically affected the spatial-cognitive strategies that mice use to locate the platform during reversal learning. These behavioral and cognitive defects coincided with changes in cortical functional connectivity (FC) and hippocampal neuroplasticity. FC between various cortical regions was assessed by resting-state fMRI (rsfMRI) methodology, and mice that had received QA injection into mPFC showed increased FC between various cortical regions. mPFC and hippocampus (HC) are anatomically as well as functionally linked as part of a cortical network that controls higher-order cognitive functions. Together, these observations demonstrate the central functional importance of rodent mPFC as well as the validity of QA-induced mPFC damage as a preclinical rodent model of the early stages of neurodegeneration.

Original languageEnglish
Article number36489
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 7 Nov 2016
Externally publishedYes

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Reversal Learning
Quinolinic Acid
Neuronal Plasticity
Aptitude
Prefrontal Cortex
Injections
Rodentia
Chemical Models
Water
Long-Term Potentiation
Brain Diseases
Tryptophan
Neurodegenerative Diseases
Cognition
Hippocampus
Magnetic Resonance Imaging

ASJC Scopus subject areas

  • General

Cite this

Quinolinic acid injection in mouse medial prefrontal cortex affects reversal learning abilities, cortical connectivity and hippocampal synaptic plasticity. / Latif-Hernandez, Amira; Shah, Disha; Ahmed, Tariq; Lo, Adrian C.; Callaerts-Vegh, Zsuzsanna; Van Der Linden, Annemie; Balschun, Detlef; D'Hooge, Rudi.

In: Scientific Reports, Vol. 6, 36489, 07.11.2016.

Research output: Contribution to journalArticle

Latif-Hernandez, Amira ; Shah, Disha ; Ahmed, Tariq ; Lo, Adrian C. ; Callaerts-Vegh, Zsuzsanna ; Van Der Linden, Annemie ; Balschun, Detlef ; D'Hooge, Rudi. / Quinolinic acid injection in mouse medial prefrontal cortex affects reversal learning abilities, cortical connectivity and hippocampal synaptic plasticity. In: Scientific Reports. 2016 ; Vol. 6.
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