In this chapter, we have covered a topic of pronounced importance—disorders of human cognition, specifically related to memory formation. We saw three examples of convergence of basic memory research with clinical investigation, highlighting neurofibromatosis mental retardation, Angelman Syndrome, and Fragile X mental retardation. It is quite striking how the detailed analysis of the basic signal transduction mechanisms underlying rodent learning and memory have converged upon many of the same molecular systems recently identified using human genetic characterization approaches in the study of mental retardation syndromes. I am cautiously optimistic that this convergence will ultimately lead to an improvement of the human condition, by identifying new therapeutic approaches to treating mental retardation.
On the abstract, intellectual side, the findings we have covered in this chapter also have interesting cognitive neurobio-logical implications. It appears that the last decades of parsing the esoteric details of synaptic plasticity and rodent memory mechanisms may well have lived up to its promise. In my opinion, it is not too early to begin to think of the types of mechanisms we have been covering in this book in the context of giving insights into human cognitive processing as well. The convergence of human and basic studies onto the same molecular cascades suggests that, indeed, we may be in the process of generating insights into the molecular basis of human cognition.
This line of thinking raises an interesting issue as well: the distinction between a developmental necessity for the gene products versus an acute, ongoing necessity as part of the signal transduction mechanisms subserving cognition. Many of the mutations we have discussed do not lead to gross morphological changes in the human CNS. Moreover, mouse studies, where available, indicate that baseline synaptic transmission is normal after loss of these gene products. These observations are consistent with a necessity for an ongoing need for the gene products in human learning and memory. In addition, in the case of both the ERK/CREB/CBP system and the CaMKII system, there is direct evidence from animal studies that acute inhibition of these systems in adults is sufficient to cause learning deficiencies. These types of considerations suggest a rethinking of our outlook on human learning disorders, changing from the traditional view of them as purely developmental problems to a new view of them as cognitive deficiencies. This sea-change in outlook may be one of the most important outcomes of new and ongoing discoveries concerning the basic signal transduction processes subserving learning and memory.
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