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: 31.38). 03/2009; 10(2):126-40. DOI: 10.1038/nrn2572
Source: PubMed

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.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neurologically-complex species utilize two intricately-coupled information–processing systems to adapt to their social and natural environments. Action potentials (APs) facilitate rapid responses to the nearly continuous fluctuations in the animal's surroundings. By contrast, genetic encodings comprise a molecular memory of ancient adaptive responses expressed as cognitive, emotional, or behavioral phenotypes. The linking of the two systems via intracellular Ca2+ networks which address transcription factors---e.g., cAMP response element-binding protein (CREB)---is an appropriate focus for the biology of human behavior. Computational modeling utilizing Boolean networks (BNs) is a suitable qualitative method, requiring no kinetic information, for eliciting the systems’ architectural properties. In particular, BNs can reveal critical intracellular regimes of possible evolutionary significance. As a platform for future research, we propose that those networks sufficiently robust to attenuate damaging intracellular noise and deleterious mutations, yet sufficiently close to chaos to permit or amplify adaptive noise and favorable mutations, would be favored by natural selection. Critical regimes of this type would be, literally, “poised for survival”, and would stabilize and promote the survival of their correlated cultural phenotypes.
    The International Journal of Biochemistry & Cell Biology 01/2015; DOI:10.1016/j.biocel.2015.01.013 · 4.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Glia are starting to be accepted as the equal of neurons. Glia's role in stress and disease as well as the latest glial modulators are reviewed. Environmental enrichment and exercise can increase intelligence, a buffer against stress, most likely via glial involvement. Cerebral dominance is also related to how glia respond to stress resulting in psychiatric illness. Glial effects on depression and schizophrenia are reviewed. Astrocytes, microglia, NG2 cells, and oligodendrocytes all contribute. Suicidal ideation can increase the permeability of the BBB resulting in the increase in serum levels of a glial protein S100B that has become a marker for the intensity of suicidal risk. Microglia form one of the bases of the inflammatory theory of psychiatric disorders. Minocycline, adenosine and cAMP inhibitors, such as PDE-4 inhibitors, have been used to modulate the microglia, with positive results in psychiatric illness. Controlling the microglia can even be protective against drug abuse. Recently a "glymphatic" system has been discovered in mice that if applicable to humans means that we clean out our brains in sleep.
    Psychiatric Clinics of North America 12/2014; 37(4):679-705. DOI:10.1016/j.psc.2014.08.003 · 2.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The go-to cognitive enhancers of today are those that are widely available rather than optimal for the user, including drugs typically prescribed for treatment of ADHD (e.g., methylphenidate) and sleep disturbances such as narcolepsy (modafinil). While highly effective in their intended therapeutic role, performance gains in healthy populations are modest at best and profoundly inconsistent across subgroups and individuals. We propose a method for in silico screening of possible novel cognitive enhancers followed by high-throughput in vivo and in vitro validation. The proposed method uses gene expression data to evaluate the the collection of activated or suppressed signaling pathways in tissues or neurons of the cognitively enhanced brain. An algorithm maps expression data onto signaling pathways and quantifies their individual activation strength. The collective pathways and their activation form what we term the signaling pathway cloud, a biological fingerprint of cognitive enhancement (or any other condition of interest). Drugs can then be screened and ranked based on their ability to minimize, mimic, or exaggerate pathway activation or suppression within that cloud. Using this approach, one may predict the efficacy of many drugs that may enhance various aspects of cognition before costly preclinical studies and clinical trials are undertaken.
    Frontiers in Systems Neuroscience 02/2015; 9. DOI:10.3389/fnsys.2015.00004

Full-text (2 Sources)

Available from
Jun 16, 2014