C. Zacher

Alterations in neuronal morphology occur in the brain during normal aging, but vary depending on neuronal cell types and brain regions. Such alterations have been related to memory and cognitive impairment. Changes in hippocampal spine densities are thought to represent a morphological correlate of altered brain functions associated with hippocampal-dependent learning and memory. We therefore have analyzed the impact of aging on different hippocampal-dependent learning tasks and on changes in dendritic spines of CA1 hippocampal and dentate gyrus neurons by analyzing adult (6-7 months) and aged (21-22 months) C57/Bl6 mice. We found a significant decrease in spine numbers of basal CA1 dendrites and decreases in spine length of apical dendrites of CA1 and dentate gyrus neurons. Furthermore, aged mice exhibited significant deficits in hippocampus-dependent learning tasks, such as the probe trial of the Morris water maze and T maze learning. Given the fact that there is no neuronal loss in the hippocampus in aged mice (von Bohlen und Halbach and Unsicker [2002] Eur. J. Neurosci. 16:2434-2440), we suggest that the memory and cognitive decline in the context of aging may be accompanied by rather subtle anatomical changes, such as numbers and morphology of dendritic spines.

Using specific polyclonal antisera against c-Fos, JunB, c-Jun and JunD, we tried to identify the candidate transcription factors of the immediate early gene family which may contribute to the molecular processes during contextual memory reconsolidation. For that purpose we analyzed the expression of these proteins in the hippocampus after contextual memory retrieval in a mouse model of fear conditioning. A single exposure to a foot shock of 0.8 mA was sufficient to induce robust contextual fear conditioning in C57BI/6N mice. In these mice context dependent memory retrieval evoked a marked induction of c-Fos and JunB, but not of c-Jun and JunD, in pyramidal CA1 neurons of the dorsal hippocampus. In contrast, mice exposed and re-exposed only to the context, without foot shock, did not show behavioral signs of contextual fear conditioning and exhibited significantly less expression of c-Fos and JunB in CA1 neurons. Mice which received a foot shock but were not re-exposed to the context revealed no immediate early gene induction. These results demonstrate that contextual memory retrieval is associated with de novo synthesis of specific members of the Fos/Jun transcription factor family. Therefore we suggest that these genes may contribute to plasticity and reconsolidation accompanying the retrieval process. The specific activation of CA1 neurons during the retrieval of contextual fear associations supports the postulated concept of a mnemonic role of this hippocampal subsector during the retrieval of contextual informations.