The molecular and cellular biology of enhanced cognition

Department of Neurobiology, Brain Research Institute, University of California, Los Angeles, California 90095, USA.
Nature Reviews Neuroscience (Impact Factor: 31.43). 03/2009; 10(2):126-40. DOI: 10.1038/nrn2572
Source: PubMed


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.

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Available from: Yong-Seok Lee, Jun 11, 2014
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    • "The iGluRs are the ligand-gated ion channels regulating cation influx for excitatory synapses and they are subdivided into N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate (KA) receptors [39, 40]. In general, the iGuRs mediate synaptic plasticity leading to a long-term potentiation (LTP) [41, 42]. In embryonic brain and neurogenic zone of adult brain, the iGluRs are highly expressed and involved in regulation of neural development and neurogenesis [43– 49]. "
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    ABSTRACT: Most studies of IR effects on neural cells and tissues in the brain are still focused on loss of neural stem cells. On the other hand, the effects of IR on neuronal differentiation and its implication in IR-induced brain damage are not well defined. To investigate the effects of IR on C17.2 mouse neural stem-like cells and mouse primary neural stem cells, neurite outgrowth and expression of neuronal markers and neuronal function-related genes were examined. To understand this process, the signaling pathways including PI3K, STAT3, metabotrophic glutamate receptor 1 (mGluR1) and p53 were investigated. In C17.2 cells, irradiation significantly increased the neurite outgrowth, a morphological hallmark of neuronal differentiation, in a dose-dependent manner. Also, the expression levels of neuronal marker proteins, β-III tubulin were increased by IR. To investigate whether IR-induced differentiation is normal, the expression of neuronal function-related genes including synaptophysin, a synaptic vesicle forming proteins, synaptotagmin1, a calcium ion sensor, γ-aminobutyric acid (GABA) receptors, inhibitory neurotransmitter receptors and glutamate receptors, excitatory neurotransmitter receptors was examined and compared to that of neurotrophin-stimulated differentiation. IR increased the expression of synaptophysin, synaptotagmin1 and GABA receptors mRNA similarly to normal differentiation by stimulation of neurotrophin. Interestingly, the overall expression of glutamate receptors was significantly higher in irradiated group than normal differentiation group, suggesting that the IR-induced neuronal differentiation may cause altered neuronal function in C17.2 cells. Next, the molecular mechanism of the altered neuronal differentiation induced by IR was studied by investigating signaling pathways including p53, mGluR1, STAT3 and PI3K. Increases of neurite outgrowth, neuronal marker and neuronal function-related gene expressions by IR were abolished by inhibition of p53, mGluR-1, STAT3 or PI3K. The inhibition of PI3K blocked both p53 signaling and STAT3-mGluR1 signaling but inhibition of p53 did not affect STAT3-mGluR1 signaling in irradiated C17.2 cells. Finally, these results of the IR-induced altered differentiation in C17.2 cells were verified in ex vivo experiments using mouse primary neural stem cells. In conclusion, the results of this study demonstrated that IR is able to trigger the altered neuronal differentiation in undifferentiated neural stem-like cells through PI3K-STAT3-mGluR1 and PI3K-p53 signaling. It is suggested that the IR-induced altered neuronal differentiation may play a role in the brain dysfunction caused by IR.
    Full-text · Article · Feb 2016 · PLoS ONE
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    • "Therefore, investigations on mechanisms leading to cognitive enhancement will have both basic and translational interest. Genetic studies on animal models have already offered a catalog of molecular alterations that result in enhanced cognition (Lee and Silva, 2009). Notably, most of these genetic changes can be related more or less directly with the process of synaptic plasticity, particularly long-term potentiation (LTP) and long-term depression (LTD). "
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    ABSTRACT: The concept of improving cognitive performance is particularly enticing, not just to ameliorate mental illness or slow-down physiological cognitive decline with aging, but also to enhance our natural cognitive abilities. There has been considerable progress in understanding the neuronal mechanisms that support higher cognitive functions, including learning and memory. A central aspect of these mechanisms is synaptic plasticity. A large amount of mechanistic information is now available on the molecules and intracellular signaling processes mediating synaptic plasticity, and by inference, cognitive function. In this chapter we will highlight a few molecular or pharmacological manipulations that have been shown to improve cognitive performance in animals, and in some cases, in humans. These examples will be organized around three major steps of the synaptic plasticity process: induction of plasticity via activation of NMDA receptors, modulation of intracellular signaling pathways triggered by activity, and expression of synaptic changes via regulation of AMPA receptor function.
    Full-text · Article · Dec 2015
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    • "an electric shock to develop conditioned responses (Kim & Fanselow 1992; Lee & Silva 2009). During the training sessions, mice were subjected to a tone paired with a mild foot shock in a conditioning chamber. "
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    Full-text · Article · Apr 2015 · Animal cells and systems the official publication of the Zoological Society of Korea
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