The effects of glutamate receptor agonists and antagonists on mouse hypothalamic and hippocampal neuronal activity shown through manganese enhanced MRI.

Manganese enhanced MRI (MEMRI) is an imaging paradigm that can be used to assess neuronal activity in vivo. Here we investigate, through the use of MEMRI, the influence of receptor dynamics on neuronal activity in the hypothalamus and hippocampus focusing on the glutamate receptor signalling system. We demonstrate that intraperitoneal (i.p.) administration of monosodium glutamate (MSG) and the ionotropic glutamate receptor (iGluR) agonists NMDA and AMPA resulted in significantly increased signal intensity (SI) in the arcuate nucleus (ARC), the suprachiasmatic nucleus (SCN) and the CA3 region of the hippocampus of mice consistent with increased neuronal activity. Administration of the NMDA receptor antagonist MK-801 resulted in significantly decreased SI in the paraventricular nucleus (PVN) consistent with decreased neuronal activity. Co-administration of MSG and the AMPA receptor antagonist NBQX attenuated the increase in SI observed in the ARC from MSG alone, suggesting MEMRI may be applicable to the study of receptor dynamics in vivo. We also observed that administration of the various iGluR agonists and antagonists modulated SI in the lateral ventricle and that high dose MSG (300 mg) caused a hitherto unseen enhancement in SI in the entire cortical/subarachnoid region. In conclusion, MEMRI reveals changes in neuronal activity in response to iGluR agonists and antagonists in the CNS in vivo as well as revealing multifaceted effects beyond those attributable to neuronal activity alone.