The molecular and cellular biology of enhanced cognition

Abstract

Most molecular and cellular studies of cognitive function have focused on either normal or pathological states, but recent research with transgenic mice has started to address the mechanisms of enhanced cognition. These results point to key synaptic and nuclear signalling events that can be manipulated to facilitate the induction or increase the stability of synaptic plasticity, and therefore enhance the acquisition or retention of information. Here, we review these surprising findings and explore their implications to both mechanisms of learning and memory and to ongoing efforts to develop treatments for cognitive disorders. These findings represent the beginning of a fundamental new approach in the study of enhanced cognition.A number of psychiatric and neurological disorders, such as Alzheimer's disease 1 , schizophrenia 2 , depression 3 , Parkinson's disease 4 , learning disabilities 5 , age-related cognitive decline 6 and mental retardation 7 are associated with learning and memory (L&M) impairments. The dominant paradigm for the development of treatments for these disorders is based on the idea that insights into the specific mechanisms that underlie each of these conditions will lead to the development of targeted interventions. The problem with this approach is that there are a large number of different causes for cognitive deficits. Genetic analyses of schizophrenia and depression, two disorders that are associated with significant cognitive impairments, have shown that they are caused by numerous mutations and many developmental and environmental factors. Similar genetic heterogeneity has been demonstrated in every other major cause for cognitive deficits, including Alzheimer's disease, learning disabilities, mental retardation and age-related cognitive decline. Thus, developing targeted therapies for each of the multiple causes of these conditions will be a formidable task. Even if targeted therapies for one or more of these specific genetic conditions are forthcoming, it is unlikely that they will have a significant impact on the cognitive impairments thought to afflict more than one in 20 people worldwide. Therefore, in addition to the prevalent targeted therapy approach, there is a need to develop alternative strategies that could have a more general impact on cognition. One possibility would be to develop strategies to ameliorate cognitive deficits irrespective of their specific genetic or environmental cause. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAlthough there is considerable evidence for animals and people with dramatic cognitive enhancements 8,9 , mechanistic studies of exceptional cognition are relatively rare. Remarkably, transgenic and KO studies in mice have revealed a surprisingly large number of mutations that seem to enhance cognitive function (TABLE 1). These mutations target a number of different signalling pathways and affect a plethora of behaviours. Surprisingly, nearly all of them seem to enhance a form of synaptic plasticity referred to...

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