Accuracy of hippocampal network activity is disrupted by neuroinflammation: Rescue by memantine

S. Rosi, V. Ramirez-Amaya, A. Vazdarjanova, E. E. Esparza, P. B. Larkin, J. R. Fike, G. L. Wenk, C. A. Barnes

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Understanding how the hippocampus processes episodic memory information during neuropathological conditions is important for treatment and prevention applications. Previous data have shown that during chronic neuroinflammation the expression of the plasticity related behaviourally-induced immediate early gene Arc is altered within the CA3 and the dentate gyrus; both of these hippocampal regions show a pronounced increase in activated microglia. Low doses of memantine, a low to moderate affinity open channel uncompetitive N-Methyl-d-aspartate receptor antagonist, reduce neuroinflammation, return Arc expression to control levels and attenuate cognitive deficits induced by lipopolysaccharide. Here we investigate whether neuroinflammation affects the accuracy of information processing in the CA3 and CA1 hippocampal regions and if this is modified by memantine treatment. Using the immediate early gene-based brain-imaging method called cellular analysis of temporal activity by fluorescence in situ hybridization, it is possible to detect primary transcripts at the genomic alleles; this provides exceptional temporal and cellular resolution and facilitates the mapping of neuronal activity. Here, we use this method to compare the neuronal populations activated by two separate experiences in CA1 and CA3 and evaluate the accuracy of information processing during chronic neuroinflammation. Our results show that the CA3 pyramidal neuron activity is not stable between two exposures to the same environment context or two different contexts. CA1 networks, however, do not differ from control conditions. These data suggest that during chronic neuroinflammation, the CA3 networks show a disrupted ability to encode spatial information, and that CA1 neurons can work independently of CA3. Importantly, memantine treatment is able to partially normalize information processing in the hippocampus, suggesting that when given early during the development of the pathology memantine confers neuronal and cognitive protection while indirectly prevents pathological microglial activation.

Original languageEnglish (US)
Pages (from-to)2464-2477
Number of pages14
JournalBrain
Volume132
Issue number9
DOIs
StatePublished - Sep 1 2009

Fingerprint

Memantine
Automatic Data Processing
Immediate-Early Genes
Hippocampus
Hippocampal CA3 Region
Hippocampal CA1 Region
Aptitude
Episodic Memory
Pyramidal Cells
Dentate Gyrus
Microglia
Fluorescence In Situ Hybridization
Neuroimaging
Lipopolysaccharides
Alleles
Pathology
Neurons
Population

Keywords

  • Hippocampal networks
  • Immediate early gene
  • NMDARs modulation
  • Neuroinflammation

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Rosi, S., Ramirez-Amaya, V., Vazdarjanova, A., Esparza, E. E., Larkin, P. B., Fike, J. R., ... Barnes, C. A. (2009). Accuracy of hippocampal network activity is disrupted by neuroinflammation: Rescue by memantine. Brain, 132(9), 2464-2477. https://doi.org/10.1093/brain/awp148

Accuracy of hippocampal network activity is disrupted by neuroinflammation : Rescue by memantine. / Rosi, S.; Ramirez-Amaya, V.; Vazdarjanova, A.; Esparza, E. E.; Larkin, P. B.; Fike, J. R.; Wenk, G. L.; Barnes, C. A.

In: Brain, Vol. 132, No. 9, 01.09.2009, p. 2464-2477.

Research output: Contribution to journalArticle

Rosi, S, Ramirez-Amaya, V, Vazdarjanova, A, Esparza, EE, Larkin, PB, Fike, JR, Wenk, GL & Barnes, CA 2009, 'Accuracy of hippocampal network activity is disrupted by neuroinflammation: Rescue by memantine', Brain, vol. 132, no. 9, pp. 2464-2477. https://doi.org/10.1093/brain/awp148
Rosi, S. ; Ramirez-Amaya, V. ; Vazdarjanova, A. ; Esparza, E. E. ; Larkin, P. B. ; Fike, J. R. ; Wenk, G. L. ; Barnes, C. A. / Accuracy of hippocampal network activity is disrupted by neuroinflammation : Rescue by memantine. In: Brain. 2009 ; Vol. 132, No. 9. pp. 2464-2477.
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