Behaviorally-induced immediate early gene Arc expression in the entorhinal cortex of the rat: deep versus superficial layers.
1. Physical Therapy an Neurological Surgery, Univ. California San Francisco, San Francisco, CA;
2. Psychology, Ohio State Univ., Columbus, OH;
3.ARL NSMA
4. Evelyn F. McKnight Brain Inst., Univ. Arizona, Tucson, AZ
The entorhinal cortex (EC) plays a crucial role as a gateway connecting the neocortex and the hippocampal formation. Layer II of the EC is a major source of excitatory input to the granule cells of the dentate gyrus (DG) and pyramidal cells of the CA3 region of the hippocampus. Furthermore, EC layer IV receives a major hippocampal efferent projection. In addition, layer III of the EC projects directly to the CA1 area of the hippocampus. Because the entorhinal-hippocampal system is a major contributor to the networks involved in long term memory, it is important to understand the input-output interactions between these structures. The immediate-early gene Arc is transcribed in neurons that are part of stable neural networks activated during spatial exploratory behaviors, Arc protein is required for the maintenance of long-term potentiation and memory consolidation (Guzowski et al., 2000), and Arc expression has been utilized to map neuronal networks important for information processing (Guzowski et al., 1999). Previous studies have demonstrated that during experimentally-induced neuroinflammation, the number of neurons expressing Arc within CA3 and DG is significantly increased as compared to control animals with no inflammation-induced treatment (Rosi et al., 2005). The current study was designed to examine behaviorally-induced Arc expression in both normal young animals and animals that had experimentally-induced neuroinflammation to further investigate how the input-output relations of the entorhinal-hippocampal system are affected by this treatment. Preliminary results from this work suggest that, following exploration of a novel environment, significantly more Arc-positive pyramidal neurons are found in the EC cortex of normal rats compared to the caged control animals. Notably, 30 min after exploration of a novel environment, about 35% of the neurons in superficial layers II and III are Arc-positive, while only about 15% of the neurons in the deep layers IV and V are activated. During chronic neuroinflammation the superficial layers of the EC showed a percentage of neurons expressing Arc comparable to control exploring animals. In contrast, in the deep layers of the EC there was a significantly lower percentage of cells that showed behaviorally-induced Arc in the LPS-treated rats. These data are consistent with the suggestion that the altered dynamics of Arc expression in the EC during chronic neuroniflammation could result, at least in part, from altered hippocampal output to deep layers of the entorhinal cortex.
Grant/Other Support: AG009219; state of Arizona and ADHS; McKnight Brain Research Foundation; AG010546; UCSF and UCSF Academic Senate Grant
Keyword (Complete): neuroinflammation; hippocampus; networks