Gene expression during memory formation.
For several decades, neuroscientists have provided many clues that point out the involvement of de novo gene expression during the formation of long-lasting forms of memory. However, information regarding the transcriptional response networks involved in memory formation has been scarce and fragmented. With the advent of genome-based technologies, combined with more classical approaches (i.e., pharmacology and biochemistry), it is now feasible to address those relevant questions--which gene products are modulated, and when that processes are necessary for the proper storage of memories--with unprecedented resolution and scale. Using one-trial inhibitory (passive) avoidance training of rats, one of the most studied tasks so far, we found two time windows of sensitivity to transcriptional and translational inhibitors infused into the hippocampus: around the time of training and 3-6 h after training. Remarkably, these periods perfectly overlap with the involvement of hippocampal cAMP/PKA (protein kinase A) signaling pathways in memory consolidation. Given the complexity of transcriptional responses in the brain, particularly those related to processing of behavioral information, it was clearly necessary to address this issue with a multi-variable, parallel-oriented approach. We used cDNA arrays to screen for candidate inhibitory avoidance learning-related genes and analyze the dynamic pattern of gene expression that emerges during memory consolidation. These include genes involved in intracellular kinase networks, synaptic function, DNA-binding and chromatin modification, transcriptional activation and repression, translation, membrane receptors, and oncogenes, among others. Our findings suggest that differential and orchestrated hippocampal gene expression is necessary in both early and late periods of long-term memory consolidation. Additionally, this kind of studies may lead to the identification and characterization of genes that are relevant for the pathogenesis of complex psychiatric disorders involving learning and memory impairments, and may allow the development of new methods for the diagnosis and treatment of these diseases.
Instituto de Biología Celular y Neurociencia Eduardo de Robertis, Facultad de Medicina, Universidad de Buenos Aires, (1113) Buenos Aires, Argentina.
Lionel Muller
LM
Igaz
Pedro
P
Bekinschtein
Monica M R
MM
Vianna
Ivan
I
Izquierdo
Jorge H
JH
Medina
D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal; D003214:Conditioning, Classical / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007266:Inhibition, Psychological; D008568:Memory / Q000502:physiology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D000546:Amanitins; D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D000841:Anisomycin