Activation Pattern of the Limbic System Following Spatial Learning Under Stress

Anatomical evidence suggests an interplay between the dorsal CA1 of the hippocampus (CA1), the basolateral amygdala (BLA) and the entorhinal cortex (EC), but their specific interactions in the context of emotional memory remain obscure. Here, we sought to elucidate the activation pattern in these areas following spatial learning under different stress conditions in the Morris water maze, using cAMP response element-binding protein (CREB) activation as a marker. Stress levels were manipulated by maintaining the water maze at one of two different temperatures: lower stress (warm water) or higher stress (cold water). Three groups of animals were tested under each condition: a Learning group, trained in the water maze with a hidden escape platform; a No-Platform group, subjected to the maze without an escape platform; and a Naïve group. To evaluate the quality of the spatial memory formed, we also tested long-term memory retention of the initial location of the platform following an interference procedure (reversal training). In the CA1 and EC, we found different CREB activation patterns for the lower- and higher-stress groups. By contrast, in the BLA a similar pattern of activation was detected under both stress levels. The data reveal a difference in the sensitivity of the memory to interference, with reversal training interference affecting the memory of the initial platform location only under the higher-stress condition. The results suggest that stress-dependent alterations in limbic system activation patterns underlie differences in the quality of the memory formed.