Dissociable influences of NR2B-receptor related neural transmission on functions of distinct associative basal ganglia circuits.
Glutamate is an important excitatory neurotransmitter within functional prefrontal-basal ganglia loops. These distinct loops mediate different cognitive functions. One function of the anterior-cingulate loop is error processing. One function of the orbito-frontal loop is response inhibition. These functions are altered in several neuro-psychiatric disorders like Huntington's disease (HD). Because of the known role of the GRIN2B C2664T polymorphism in HD neuropathology, which is partly due to increased glutamatergic neural transmission, we analyze how this polymorphism influences error processing and response inhibition in a sample of healthy probands (N=65). Combining a genetic approach with event-related potential (ERP) measurements of response inhibition (OFC-loop function) and error processing (ACC-loop function), we provide robust results showing a selective modulation of response inhibition processes by the GRIN2B C2664T polymorphism at the behavioural and neurophysiological level. Response inhibition processes were stronger in the CT/TT genotype group, compared to the CC genotype group. Since error processing functions were not affected, the results suggest for differential influences of the GRIN2B C2664T polymorphism on response inhibition and error processing functions. The results provide first insight into cognitive-neurophysiological effects of the GRIN2B C2664T polymorphism. The dissociation obtained may be due to a differential importance of N-methyl-D-aspartate receptors for glutamatergic neural transmission in different striatal compartments (matrix and striosomes). We provide a model on this that may be a target for future research.
Beste
Christian
C
Institute for Cognitive Neuroscience, Department of Biopsychology, Ruhr-Universität Bochum, Bochum, Germany. christian.beste@rub.de
Baune
Bernhard T
BT
Domschke
Katharina
K
Falkenstein
Michael
M
Konrad
Carsten
C
D000328:Adult; D001479:Basal Ganglia / Q000502:physiology*; D005071:Evoked Potentials; D056344:Executive Function / Q000502:physiology*; D030141:Feedback, Psychological / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D020125:Mutation, Missense; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors; D055815:Young Adult
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate