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

Abstract

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, while proximal CA1 is innervated by cells in the medial entorhinal cortex that are responsive to space. This suggests neurons in different areas along the promixodistal 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: exploration of the same environment containing the same objects twice (AA), or exploration of two different environments that contained identical objects (AB). The hypothesis was that CA1 place cells should show field remapping in the condition where 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. In old rats, however, 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.

Head west or left, east or right: interactions between memory systems in neurocognitive aging

“…We and others (Fletcher et al, 2014; Hartzell et al, 2013) have found that resting, baseline levels of Arc messenger RNA (mRNA) expression are equivalent in the young and aged hippocampus, and in the present experiments only young adult HC controls were examined (n = 5). Additionally, to distinguish the effects of well-established place and response learning from activation induced by the cognitive demands of the WDS, other controls received continued training on only one of the task strategies.…”

Hippocampal Formation

“…Combined with the differential distribution of inputs from MEC and LEC to proximal and distal CA1 respectively, this connectivity provides strong evidence for functional differences along the transverse axis. Functional differences along the proximodistal axis of CA1 related to spatial information content (Henriksen et al, 2010;Hartzell et al, 2013) support this notion. Functional differences along the CA3 transverse axis have also been reported (Sauvage et al, 2013).…”

CA1 pyramidal cell diversity enabling parallel information processing in the hippocampus

“…The medial and lateral entorhinal cortices (MEC and LEC, respectively) provide dual input streams into the hippocampus 31 , with the MEC providing predominantly spatial information and the LEC providing primarily nonspatial information to CA1PCs 31–33 . In this pathway, MEC and LEC project to different parts of CA1 along the proximodistal axis, leading to differential recruitment of PCs along this axis during spatial and nonspatial tasks 47,75,76,78,80,91,92 . A recent study 93 found that these two inputs also activate the radial CA1PC sublayers differentially (Fig.…”