One-trial aversive learning induces late changes in hippocampal CaMKIIalpha, Homer 1a, Syntaxin 1a and ERK2 protein levels.
Most studies regarding altered gene expression after learning are performed using multi-trial tasks, which do not allow a clear discrimination of memory acquisition, consolidation and retrieval. We screened for candidate memory-modulated genes in the hippocampus at 3 and 24 h after one-trial inhibitory avoidance (IA) training, using a cDNA array containing 1176 genes. While 33 genes were modulated by training (respect to shocked-only animals), most of them were upregulated (27 genes) and only 6 were downregulated. To confirm and extend these findings, we performed RT-PCRs and analyzed differences in protein levels in rat hippocampus using immunoblot assays. We found several proteins upregulated 24 h after training: extracellular signal-regulated kinase ERK2, Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIalpha), Syntaxin 1a, c-fos and Homer 1a. The total level of none of these proteins were found to be altered when measured 3-h post-training. Several of the mRNAs corresponding to the upregulated proteins were changed at 3 h but not 24 h. Additionally, a number of other candidates were identified for the first time as modulated by learning. The results presented here suggest that single-trial tasks can expose previously unseen differences in dynamic regulation of gene expression after behavioral manipulations, both at the transcriptional and translational levels, and reveal a diversity of gene products modulated by this task, allowing deeper understanding of the molecular basis of memory formation.
Igaz
Lionel Müller
LM
Instituto de Biologia Celular y Neurociencias, Facultad de Medicina, UBA, Paraguay 2155, piso 3, 1121 Buenos Aires, Argentina.
Bekinschtein
Pedro
P
Izquierdo
Iván
I
Medina
Jorge H
JH
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001362:Avoidance Learning / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D000072233:Homer Scaffolding Proteins; D008297:Male; D008568:Memory / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050827:Syntaxin 1; D013997:Time Factors; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D000954:Antigens, Surface; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C494213:Stx1a protein, rat; D050827:Syntaxin 1; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517675:Camk2a protein, rat; D019950:Mitogen-Activated Protein Kinase 1