The entry of manganese ions into the brain is accelerated by the activation of N-methyl-D-aspartate receptors

Itoh, K., et al. "The entry of manganese ions into the brain is accelerated by the activation of< i> N-methyl-d-aspartate receptors." Neuroscience 154.2 (2008): 732-740. There are many advantages of using MeMRI to study in vivo neuronal activity. However, there is the disadvantage of having to anesthetize the animal during the imaging which has an effect on overall brain functioning. Previous studies done by Lin/Koretsky and Aoki have demonstrated that manganese enhancement in MR images is dampened the deeper an animal is in anesthesia. That being said, no studies had been done looking at effects of manganese enhancement across different methods of anesthesia until Itoh in this study in 2008. They found that most anesthetics including isoflurane, urethane, and pentabarbitol did not have significant affects on manganese enhancement. Where as the use of ketamine significantly decreased manganese enhanced contrast. Unlike the other anesthetic that act by potentiating GABAergic pathways, ketamine acts as a partial antagonist for NMDA receptors. An NMDAR under natural conditions is acted upon by glutamate to then activate glutamatergic neurons via the influx of calcium. The observation of decreased manganese enhancement in the presence of ketamine then led to further questions about the entry of systemic manganese into the cerebral spinal fluid and eventually brain tissue. Using various NMDA, GABAa, and AMPA agonists and antagonists this study found that NMDAR mediated glutamatergic excitation plays a major role in influencing manganese enhancement in MRI. Both NMDAR antagonist significantly decreased manganese enhancement within the ventricles (other brain regions did not show differences because images were only taken up to three hours post MnCl2 injections). Oppositely, NMDAR agonist produced significantly increased manganese enhancement compared to controls. AMPA antagonist did not appear to change manganese enhancement, while GABAa antagonist also produced increased manganese enhancement. A limitation to this study is that they did not address effects resulting from changes in the NMDARs within brain tissue itself, which is important to our studies looking at plasticity in neuronal activity in the RVLM of sedentary and physically active rats. I would hypothesized by extrapolating from this study however, that sinoaortic dennervated rats will show an increase in manganese enhancement within the RVLM when compared to the non-dennervated control animals. ~JI