Exploration induces hippocampus-independent up-regulation of Arc in layer V of mouse medial entorhinal cortex

Neurons in medial entorhinal cortex (MEC) encode an animal’s position in space and are the main path for routing information between the neocortex and hippocampus. Superficial layers of the MEC project to the hippocampus, whereas deep layers are believed to be primarily driven by hippocampal output. The activityregulated cytoskeleton-associated protein, Arc, is a marker of neuronal activity and is necessary for forms of plasticity and spatial learning. Its expression pattern may therefore provide insight into the MEC networks involved in typical spatial behaviours. Using mice that express an enhanced GFP construct under the control of the endogenous Arc promoter (Wang et al., 2006), we investigated changes in the spatial patterns of both active Arc transcription and protein expression following exposure to a novel environment. We show that Arc expression in MEC is very low in naïve animals. Exposing animals to a novel environment significantly up-regulates GFP and Arc protein expression in MEC layer V, but not in in MEC layer II. Up-regulation of GFP and Arc protein expression is also evident across visual cortex. Using ibotenic acid-induced lesions of the CA1 region of hippocampus, we found that up-regulation of Arc in MEC layer V does not depend on input from dorsal CA1. This result contrasts with the long-held view that the major input to MEC is from the hippocampus, via deep layers of the MEC. It will be important to identify the neurons that provide the inputs responsible for increased Arc expression and the cell populations in which it occurs.