INVESTIGADORES
BEKINSCHTEIN Pedro Alejandro
artículos
Título:
Gene expression during memory formation
Autor/es:
LIONEL MÜLLER IGAZ; PEDRO BEKINSCHTEIN; MONICA R. VIANNA; IVAN IZQUIERDO; JORGE H. MEDINA
Revista:
NEUROTOXICITY RESEARCH
Referencias:
Año: 2004 vol. 6 p. 189 - 204
ISSN:
1029-8428
Resumen:
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.