A recently reported rapid potentiation of NMDA receptors by Group I metabotropic glutamate receptors (mGluRIs) via a Homer protein link is distinct from the classical, relatively slow inhibitory G-protein-associated signaling triggered by mGluRI activation. The relationship between these two mechanisms remains unknown. Here, we focused on the mGluRI-dependent modulation of NMDAR response in hippocampal dentate gyrus granule cells and cerebellar granule cells of C57BL6-J mice and found that these two contrasting mechanisms overlap competitively on the time scale from hundreds of milliseconds to seconds, with the net effect depending on the cell type. At a shorter time interval (units of millisecond), the Homer-mediated signal from mGluRIs prevails, causing upregulation of NMDAR function, in both dentate gyrus granule cells and cerebellar granule cells. Our results shed light on the possible mechanisms of anti-schizophrenia drugs that disrupt Homer-containing protein link.
|Number of pages||16|
|Journal||Journal of Neuroscience|
|Early online date||3 Oct 2018|
|Publication status||Published - 14 Nov 2018|
- cerebellar granule cells
- dentate gyrus granule cells
- Homer protein
- inter-receptor crosstalk
- metabotropic glutamate receptors
- NMDA receptors
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- School of Medicine, Medical Sciences & Nutrition, The Rowett Institute of Nutrition and Health - Lecturer