EN
INTRODUCTION: ICER (Inducible cAMP Early Repressor) is an effective endogenous repressor of CREB/ CREM/ATF transcription factors family, including its own expression. We have developed a Syn‑Flag‑ICER II transgenic rat line. In transgenic animals, we have surprisingly detected increased levels of mRNA for CREB or CREM transcription factors. We have also detected upregulation of CREB dependent miR‑132. Nerogenesis is a process of generation and maturation of newborn neurons into neuronal networks in the developing brain. We have found that ICER II overexpressing rats showed reduced hippocampal adult neurogenesis. The number of the SGZ BrdU positive cells was similar, but in the mature granular neurons layer, the number of BrdU positive cells was decreased when compared to control animals. One of the crucial elements enabling the incorporation of newborn neurons into neuronal network of the brain is the active reorganization of the extracellular matrix mostly by action of metalloproteinases. The most known for its activity in the brain is matrix metalloproteinase 9 (MMP-9), which is also one of the known targets of miR‑132. We have examined MMP-9 activity in the ICER overexpressing rat brain lysates, and we observed decreased activity of MMP‑9 in ICER mutants as compared to WT controls. RESULTS: We have also found that ICER rats with affected neurogenesis employ different learning strategies than their control littermates in the Morris Water Maze learning paradigm. The results of this behavioral tests indicate that transgenic rats didn’t differ from controls in their learning and memory capabilities, but they showed differences in strategies of finding the hidden platform. Male ICER rats more often were choosing imprecise strategies to find the platform than control males. CONCLUSIONS: Those results demonstrate that disruption of CREB dependent gene expression in neurons by overexpression of ICER affects adult neurogenesis and causes changes that affect discrete aspects of animal cognitive behavior.