RISC activity in hippocampus is essential for contextual memory.
RNA-Induced Silencing Complex (RISC) mediates post-transcriptional control of gene expression and contains Argonaute 2 (AGO2) protein as a central effector of cleavage or inhibition of mRNA translation. In the brain, the RISC pathway is involved in neuronal functions, such as synaptic development and local protein synthesis, which are potentially critical for memory. In this study, we examined the role of RISC in memory formation in rodents, by silencing AGO2 expression in dorsal hippocampus of C57BL/6 mice and submitting animals to hippocampus-related tasks. One week after surgery, AGO2 downregulation impaired both short-term and long-term contextual fear memories. Conversely, no long-lasting effects were observed three weeks after surgery, when AGO2 levels were re-established. These results show that altered RISC activity severely affects learning and memory processes in rodents.
Batassa
Enrico Maria
EM
Dep. of Cellular Biotechnology, and Ematology, University of Rome La Sapienza, Italy.
Costanzi
Marco
M
Saraulli
Daniele
D
Scardigli
Raffaella
R
Barbato
Christian
C
Cogoni
Carlo
C
Cestari
Vincenzo
V
D000818:Animals; D060565:Argonaute Proteins; D003213:Conditioning, Psychological; D015536:Down-Regulation; D015852:Eukaryotic Initiation Factor-2 / Q000096:biosynthesis* / Q000235:genetics; D005239:Fear; D020868:Gene Silencing; D006624:Hippocampus / Q000378:metabolism*; D008568:Memory; D008570:Memory, Short-Term; D051379:Mice; D008810:Mice, Inbred C57BL; D034743:RNA-Induced Silencing Complex / Q000502:physiology*; D013997:Time Factors
C526735:Ago2 protein, mouse; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; D034743:RNA-Induced Silencing Complex