Biomedical subjects

Christopher G Thomas

Publications and source records attributed to Christopher G Thomas.

5 recordsLinked to original sources

PubMed2005

Direct interaction of myosin regulatory light chain with the NMDA receptor.

NMDA receptors interact with a variety of intracellular proteins at excitatory synapses. In this paper we show that myosin regulatory light chain (RLC) isolated from mouse brain is a NMDA receptor-interacting protein. Myosin RLC bound directly to the C-termini of both NMDA receptor 1 (NR1) and NMDA receptor 2 (NR2) subunits, rendering the interaction of myosin RLC with NMDA receptors distinct from that of calmodulin which is considered a NR1-interacting protein. Myosin RLC co-localized with NR1 in the dendritic spines of isolated hippocampal neurons, and was co-immunoprecipitated from brain extracts in a complex with NR1, NR2A, NR2B, PSD-95, Adaptor protein-2 and myosin II heavy chain. The C0 region of NR1 was necessary and sufficient for binding myosin RLC. Ca2+/calmodulin, but not calmodulin alone, displaced recombinant myosin RLC from the carboxy tail of NR1 indicating that myosin RLC and Ca2+/calmodulin can compete for a common binding site on NR1 in vitro. Myosin RLC is the only known substrate for myosin regulatory light chain kinase, which has recently been shown to modulate NMDA receptor function in isolated hippocampal neurons. Our results suggest that an additional level of NMDA receptor regulation may be mediated via a direct interaction with a light chain of myosin II. Thus, myosin RLC-NMDA receptor interactions may contribute to the contractile and motile forces that are placed upon NMDA receptor subunits during changes associated with synaptic plasticity and neural morphogenesis.

Amino Acid Sequence↗

PubMed2004

Learning-related fMRI activation associated with a rotational visuo-motor transformation.

The unique ability to learn transformed or altered visuo-motor relationships during motor learning (visuo-motor transformation learning) has engaged researchers for over a century. Compared to other forms of motor learning (e.g., sequence learning), little is known about plasticity in the cortical and/or subcortical systems involved. We used fMRI to isolate region-specific activation changes during the learning of a visuo-motor (joystick) task under a simple transformation (90 degree rotation of visual feedback). Distributed brain systems were engaged in the learning process. In particular, we found evidence of a learning-dependent transition from early activation of the posterior parietal cortex to later distributed cortico-subcortical-cerebellar responses (in the temporal and occipital cortices, basal ganglia, cerebellum and thalamus). The role of the posterior parietal cortex may relate specifically to the acquisition of the transformation, while that of the fusiform and superior temporal gyri may reflect higher level visual and visuo-spatial processing underlying consolidation. Learning-related increases in cerebellar responses are consistent with its proposed role in the acquisition of internal models of the motor apparatus. These learning-related changes suggest a role for interacting neural systems involving the co-operation of cortico-cortico, cortico-cerebellar and cortico-basal ganglia loops during visuo-motor transformation learning.

Adult↗

PubMed2003

Flexible retinotopy: motion-dependent position coding in the visual cortex.

Although the visual cortex is organized retinotopically, it is not clear whether the cortical representation of position necessarily reflects perceived position. Using functional magnetic resonance imaging (fMRI), we show that the retinotopic representation of a stationary object in the cortex was systematically shifted when visual motion was present in the scene. Whereas the object could appear shifted in the direction of the visual motion, the representation of the object in the visual cortex was always shifted in the opposite direction. The results show that the representation of position in the primary visual cortex, as revealed by fMRI, can be dissociated from perceived location.

Attention↗

PubMed2002

Noise reduction in BOLD-based fMRI using component analysis.

Principle Component Analysis (PCA) and Independent Component Analysis (ICA) were used to decompose the fMRI time series signal and separate the BOLD signal change from the structured and random noise. Rather than using component analysis to identify spatial patterns of activation and noise, the approach we took was to identify PCA or ICA components contributing primarily to the noise. These noise components were identified using an unsupervised algorithm that examines the Fourier decomposition of each component time series. Noise components were then removed before subsequent reconstruction of the time series data. The BOLD contrast sensitivity (CS(BOLD)), defined as the ability to detect a BOLD signal change in the presence of physiological and scanner noise, was then calculated for all voxels. There was an increase in CS(BOLD) values of activated voxels after noise reduction as a result of decreased image-to-image variability in the time series of each voxel. A comparison of PCA and ICA revealed significant differences in their treatment of both structured and random noise. ICA proved better for isolation and removal of structured noise, while PCA was superior for isolation and removal of random noise. This provides a framework for using and evaluating component analysis techniques for noise reduction in fMRI.

Adult↗

PubMed2002

Calcineurin acts via the C-terminus of NR2A to modulate desensitization of NMDA receptors.

Phosphatase IIb (calcineurin, CaN) can reduce N-methyl-D-aspartate (NMDA) synaptic responses by enhancing glycine-independent desensitization. We examined the action of CaN on desensitization in recombinant NMDA receptors comprised of NMDA receptor 1 (NR1) and NR2A subunits. The C-terminus of NR2A, but not NR1, was critical for modulation of desensitization by CaN. Alanine-scanning mutagenesis indicated that serines 900 and 929 in NR2A altered desensitization, as did inhibition of tyrosine phosphatases. Our data suggest that dephosphorylation-dependent regulation of the C-terminus of NR2A increases desensitization of NMDA receptors, providing an additional mechanism for modulation of synaptic signals.

Calcineurin↗