Stability of hippocampal networks is influenced by the presence or absence of activated microglial cells.
1. Physical Therapy and Neurological Surgery, Univ. California San Francisco, San Francisco, CA;
2. Inst. of Neurobiology, UNAM, Queretaro, Mexico;
3. Psychology, Ohio State Univ., Columbus, OH;
4. ARL NSMA
5. Evelyn F. McKnight Brain Inst., Univ. Arizona, Tucson, AZ
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 disrupted within the CA3 and DG regions compared to control behaving animals. Both of these hippocampal regions show a pronounced increase in activated microglia following this treatment, an effect which may result in altered 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 in CA3, or ‘downstream’ in CA1, or whether these regions are able to compensate for this altered activity, we evaluated the expression of Arc in CA1 and CA3 pyramidal cells to two identical or different environments. Rats were chronically infused with lipopolysaccharide (LPS) (0.25 ?g/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 25 min. Using the catFISH method we can study the stability or differential response of a particular group of cells to similar or different environments, respectively. In the CA1 area, Arc mRNA expression was induced in the same group of neurons reliably after exploration of the same novel environment twice (A-A). Additionally, for the A-B condition, two different populations of CA1 neurons responded independently to the two different environments both in animals with experimentally-induced inflammation and animals infused with aCSF. Neurons in the CA3 area of the hippocampus, on the other hand, do not show discrimination through the expression of Arc, either in the A-A (similar) or A-B (distinct) environment treatments (with no cell loss apparent). These preliminary 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. CA1 is the final station in the hippocampal “trisynaptic loop”, but because of the direct input received from the entorhinal cortex, may be able to act independently of the output from CA3. These present data are consistent with the hypothesis that CA1 can detect ‘mismatches’ between the information received via CA3-DG and the enthorinal cortex, possibly allowing for more accurate information outflow to the neocortex from the subiculum.
Grant/Other Support: AG009219; state of Arizona and ADHS; McKnight Brain Research Foundation; AG010546; UCSF and UCSF Academic Senate Grant
Keyword (Complete): Arc; neuroinflammation; hippocampus; catFISH