CA1 hippocampal networks remain stable during chronic neuroiflammation.
1. NSMA, Univ Arizona, Tucson, AZ, USA
2. Instit Fisiol Cel UNAM, Mexico DF, Mexico
3. Cog Neurosci Ctr and Dept Neurol, School of Medicine, Medical College of Georgia
4. Neurosci and Neurol, John Hopkins Univ, Baltimore, MD
Neuroinflammation is associated with a variety of neurological diseases and is reliably detected by the presence of activated microglia. We previously demonstrated that during chronic neuroinflammation, behaviorally-induced expression of the immediate early gene Arc is increased within the CA3 and DG. Both of these hippocampal regions show a pronounced increase in activated microglia following this treatment, suggesting that neuroinflammation may alter the coupling of neural activity with macromolecular synthesis implicated in learning and plasticity (Rosi et al., 2005). To investigate whether the disruption of Arc expression in the DG and CA3 regions affected the stability of networks ‘downstream’ in the CA1 region, or whether this region is able to compensate for this altered activity, we evaluated the expression of Arc in CA1 pyramidal cells to two identical or different environments. Rats were chronically infused with lipopolysaccharide (LPS) (0.25 µg/hr) or artificial cerebrospinal fluid (aCSF) into the 4th ventricle for 28 days. On day 29, one subset of rats explored twice the same novel environment (A-A) or two different environments (A-B) for 5 min, separated by 30 min. Using the catFISH (compartmental analysis of temporal activity with fluorescence in situ hybridization) method we can study the stability or differential response of a particular group of cells to similar or different environments, respectively. Here we found that Arc mRNA expression was induced in the same group neurons after exploration of the same novel environment while two different populations of neurons responded to two different environments in animals with experimental induced inflammation, similar to the control animals infused with aCSF. These data suggest that the CA1 area of the hippocampus is able to compensate for the neuroinflammation-induced alteration of activity in the DG and CA3 areas, perhaps through the direct projection from the layer III entorhinal cortical input to CA1.
Support Contributed By: AG010546, AG009219, HFSP LT00112-2002-C
Key words: neurodegenerative disease, activated microglia, glutamate, Arc