Genetic variability of human cognitive function: focusing on the glutamatergic synapse
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1
Leibniz Institute for Neurobiology, Germany
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2
Charite, Germany
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3
Helmholtz Center for Neurodegenerative Diseases (DZNE), Germany
The glutamatergic synapse is the principal site of interaction between neurons in the mammalian central nervous system, and monoaminergic transmitters like dopamine and serotonin modulate the response properties of glutamatergic synapses. Numerous animal studies have provided evidence for a role of synaptic adapter and signaling molecules and in learning and memory function, and, more recently, genetic variations in these proteins have been linked to psychiatric disorders in humans. Goal: We have recently demonstrated the modulation of human hippocampus-dependent novelty processing by a genetic variation of the serotonin 2a receptor, and we now systematically investigate how synaptic scaffolding and adapter proteins influence cognitive function in the healthy human population. Methods: We study the influence of common genetic variations in pre- and perisynaptic proteins on human cognitive abilities such as attention, working memory, and episodic memory as well as on complex personality traits. Polymorphisms are chosen by potential relevance on a molecular level and by results from genome-wide association studies. Results: We have identified associations of genetic variability in presynaptic active zone proteins (Piccolo, Bassoon) and postsynaptic density adapter molecules (ProSAP2/Shank3) with memory function. We have further observed modulation of human prefrontal cortex function by genetic variability of synaptic extracellular matrix components. Conclusion: Recent GWAS linking synaptic protein genetic variability to psychiatric diseases are in good agreement with previous findings from animal research. Our work provides evidence that the genetic variations linked to psychiatric disorders might exert their effects via cognition-related endophenotypes.
Keywords:
Glutamatergic Synapse,
ProSAP2/Shank3,
serotonin 2a
Conference:
XI International Conference on Cognitive Neuroscience (ICON XI), Palma, Mallorca, Spain, 25 Sep - 29 Sep, 2011.
Presentation Type:
Symposium: Oral Presentation
Topic:
Symposium 12: Human genetics of cognition
Citation:
Schott
B,
Richter
S and
Seidenbecher
C
(2011). Genetic variability of human cognitive function: focusing on the glutamatergic synapse.
Conference Abstract:
XI International Conference on Cognitive Neuroscience (ICON XI).
doi: 10.3389/conf.fnhum.2011.207.00537
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Received:
14 Nov 2011;
Published Online:
28 Nov 2011.
*
Correspondence:
Dr. Bjorn Schott, Leibniz Institute for Neurobiology, Magdeburg, Germany, Bjoern-Hendrik.Schott@dzne.de