Transcription of the Immediate-Early Gene Arc in CA1 of the Hippocampus Reveals Activity Differences along the Proximodistal Axis That Are Attenuated by Advanced Age

The CA1 region of the hippocampus receives distinct patterns of afferent input to distal (near subiculum) and proximal (near CA2) zones. Specifically, distal CA1 receives a direct projection from cells in the lateral entorhinal cortex that are sensitive to objects, whereas proximal CA1 is innervated by cells in the medial entorhinal cortex that are responsive to space. This suggests that neurons in different areas along the proximodistal axis of CA1 of the hippocampus will be functionally distinct. The current experiment investigated this possibility by monitoring behavior-induced cell activity across the CA1 axis using Arc mRNA imaging methods that compared adult and old rats in two conditions: (1) exploration of the same environment containing the same objects twice (AA) or (2) exploration of two different environments that contained identical objects (AB). The hypothesis was that CA1 place cells should show field remapping in the condition in which environments were changed, but the extent of remapping was expected to differ between proximal and distal regions and between age groups. In fact, neurons in the proximal region of CA1 in adult animals exhibited a greater degree of remapping than did distal CA1 cells when the environment changed, suggesting that cells receiving input from the medial entorhinal cortex are more sensitive to spatial context. However, in old rats, there were no differences in remapping across the proximodistal CA1 axis. Together, these data suggest that distal and proximal CA1 may be functionally distinct and differentially vulnerable to normative aging processes.