Our laboratory focuses on the study of the neurobiological and genetic bases of cognitive processes relating to learning, memory, and emotions. Learning requires the continued ability of the brain to establish new synaptic configurations and could be viewed as the continuation of the developmental process. Disrupting the normal balance between the stable fixation of memory representations, via the establishment of strong synaptic connections, and the generation of new potential presynaptic and postsynaptic sites for use in future learning experiences could explain the perseverative responses seen in pervasive developmental disorders, such as Asperger’s Syndrome, one of the Autism Spectrum Disorders (ASDs), as well as other neuropsychiatric disorders.
Over the past 50 years, evidence has accumulated indicating that the regulation of gene expression in brain neurons is essential for the fixation of memories in the brain. Several mechanisms involved in gene expression regulation by other to be of pivotal importance for the formation of long-lasting memories in the brain. Some of these mechanisms include transcriptional and translational processes required for appropriate temporal and brain regional specific changes in gene expression associated to particular forms of learning and memory.
Experiments with rodents in our laboratory examine specific changes in gene expression and gene function as a result of learning experiences in a variety of behavioral paradigms including spatial discrimination learning, conditioned taste aversion, and fear conditioning. There are two specific lines of study:
• The role of DNA recombination and repair processes involving DNA endonucleases (Saavedra-Rodríguez et al., 2009), ligases (Wang et al., 2003; Colón-Cesario et al., 2006a), and polymerases (Peña de Ortiz et al., 2003) in long-term memory formation. Our lab has pioneered this line of research within the area of neurobiology of learning and memory. We are now completing studies in which, using state-of-the-art genomic technologies, we have identified a group of candidate target genes regulated in learning and memory by genomic rearrangement processes. The mechanism of genomic rearrangement proposed by our laboratory (Peña de Ortiz & Arshavky, 2001), postulates that the genes regulated by this process encode proteins inportant for the establishment of normal synaptic connections. Thus, dysregulation of this mechanism in the brain during development may result in improper wiring of neural neutworks thereby ausing a symtomatology that impairs individuals to perceive and interact properly with the world that surrounds them, such as in autism and schizophrenia.
• The role of Nurr1, an immediate early transcription factor regulated by the cAMP response element binding protein (CREB) and CREB-binding protein (CBP) in learning and memory processes. Nurr1 is required for the normal development of dopaminergic neurons in the mesolimbic region of the brain. Our laboratory pioneered studies demonstrated that Nurr1 is transcriptionally regulated in specific brain areas as a result of learning and memory (Peña de Ortiz et al., 2000; Ge et al., 2003). We also demonstrated that when the expression of Nurr1 in the hippocampus, a region of the brain important for learning and memory, is blocked in rats (Colón-Cesario et al., 2006b) they behave in ways that are reminiscent to how people with autism, bipolar disorder, and schizophrenia conduct themselves. Current studies are examining the importance of Nurr1 in the hippocampus for the processing of emotions.