Differential Effects of NMDA and AMPA Glutamate Receptors on Functional Magnetic Resonance Imaging Signals and Evoked Neuronal Activity during Forepaw Stimulation of the Rat

Abstract

Most of the currently used methods for functional brain imaging do not visualize neuronal activity directly but rather rely on the elicited 1-(4-aminophenyl)-3-methylcarbamyl-4-methyl7,8-methylenedioxy-3,4-dihydro-5H-2,3benzodiazepine] significantly decreased both the hemodynamic response (BOLD, Ϫ49 Ϯ 13 and Ϫ65 Ϯ 15%; PWI, Ϫ22 Ϯ 48 and Ϫ68 Ϯ 4% for 5 and 7 mg/kg, i.v., respectively; CBV, Ϫ80 Ϯ 7% for 7 mg/kg; n ϭ 4) and the SEPs (up to Ϫ60%). These data indicate that the interaction of glutamate with its postsynaptic and/or glial receptors is necessary for the generation of blood flow and BOLD responses and illustrate the differential role of NMDA-Rs and AMPA-Rs in the signaling chain leading from increased neuronal activity to the hemodynamic response in the somatosensory cortex.

NMDA-Dependent Mechanisms Only Affect the BOLD Response in the Rat Dentate Gyrus by Modifying Local Signal Processing

“…These results indicate that in the barrel cortex NMDA receptordependent mechanisms can control the local blood flow via release of cyclooxygenase-2 generated metabolites. Similar effects of NMDA receptor inhibition on local hemodynamic parameters were also observed in the somatosensory cortex during electrical stimulation of forepaw stimulation (Gsell et al, 2006) or the ramus infraorbitalis of the trigeminal nerve (Norup Nielsen and Lauritzen, 2001) and, as shown in the current fMRI study, in the entorhinal cortex during electrical perforant pathway stimulation. Consequently, NMDA receptor-dependent mechanisms may be more important for the generation of a BOLD response in cortical areas, or, more likely, the direct perforant pathway stimulation is efficient enough to trigger hemodynamic responses via additional mechanisms.…”

“…One reason could be that the applied concentration of MK801 (i.e., 0.5 mg/kg body weight ) was not sufficient enough to inhibit NMDA-dependent processes, at least during the beginning until distribution processes are completed. In the previous paper by Gsell et al (2006), an effect of MK801 on generated BOLD responses was observed with a delay of 8 to 12 minutes, indicating that in our approach an effect of MK801 should also occur during the second block after application. During the third stimulation block, we observed a significant change of the population spike augmentation and development of the population spike latency, indicating that at this time the applied concentration of MK801 was efficient enough to modify the neuronal activities (Figures 3 and 4).…”

“…Glutamate acts on ionotropic (AMPA (2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)-propanoic acid), Kainate, N-methyl-D-aspartate (NMDA)) and metabotropic (mGluR1-8) receptors, which may contribute to the generation of a BOLD response. In a previous study, NMDA receptor activation was assumed to be an essential part of the signaling chain generating the BOLD response after neuronal activation (Gsell et al, 2006). This is of particular interest because NMDA receptors are considered to be coincidence detectors and their activation is necessary for various forms of synaptic plasticity.…”

Current status of functional MRI on small animals: application to physiology, pathophysiology, and cognition

“…Various anaesthetics have been tested in rats and mice for compatibility with functional activation using haemodynamic fMRI (18)(19)(20)(21)(22).…”

“…In a recent extensive investigation, two ionotropic glutamate receptor antagonists working on either the N-methyl-D-aspartate (NMDA) subtype (NMDA-R) or the alpha-amino-3-hydroxy-5-methyl-4 isoxazole propionic acid (AMPA) subtype (AMPA-R) were applied during somatosensory forepaw stimulation in the rat, while electrical brain activity was recorded with somatosensory evoked potentials (SEPs) and haemodynamic response by BOLD-sensitive and CBF-sensitive fMRI (20). On the basis of their complex study design, these authors were able to analyze the differential effects of these two ionotropic glutamate receptor types on neuronal activity and haemodynamic response: the NMDA-R antagonist MK-801 only slightly diminished the SEPs but markedly reduced the haemodynamic response, indicating that NMDA-R-mediated neuronal excitation is closely connected to the haemodynamic response [e.g.…”