title: 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 hemodynamic and/or metabolic responses. Glutamate, the major excitatory neurotransmitter, plays an important role in the neurovascular/neurometabolic coupling, but the specific mechanisms are still poorly understood. To investigate the role of the two major ionotropic glutamate receptors [NMDA receptors (NMDA-Rs) and AMPA receptors (AMPA-Rs)] for the generation of functional magnetic resonance imaging (fMRI) signals, we used fMRI [measurements of blood oxygenation level-dependent (BOLD), perfusion-weighted imaging (PWI), and cerebral blood volume (CBV)] together with recordings of somatosensory evoked potentials (SEPs) during electrical forepaw stimulation in the alpha-chloralose anesthetized rat. Intravenous injection of the NMDA-R antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate] (0.06 mg/kg plus 3.6 microg x kg(-1) x h(-1)) significantly decreased BOLD (-51 +/- 19%; n = 5) and PWI (-57 +/- 26%; n = 5) responses but reduced the SEPs only mildly (approximately -10%). Systemic application of the AMPA-R antagonist GYKI-53655 [1-(4-aminophenyl)-3-methylcarbamyl-4-methyl-7,8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepine] significantly decreased both the hemodynamic response (BOLD, -49 +/- 13 and -65 +/- 15%; PWI, -22 +/- 48 and -68 +/- 4% for 5 and 7 mg/kg, i.v., respectively; CBV, -80 +/- 7% for 7 mg/kg; n = 4) and the SEPs (up to -60%). 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.
authors.affiliation: Max Planck Institute for Neurological Research, 50931 Cologne, Germany.
authors.forename: Willy
authors.initials: W
authors.lastname: Gsell
authors.forename: Michael
authors.initials: M
authors.lastname: Burke
authors.forename: Dirk
authors.initials: D
authors.lastname: Wiedermann
authors.forename: Gilles
authors.initials: G
authors.lastname: Bonvento
authors.forename: Afonso C
authors.initials: AC
authors.lastname: Silva
authors.forename: François
authors.initials: F
authors.lastname: Dauphin
authors.forename: Christian
authors.initials: C
authors.lastname: Bührle
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
authors.forename: Wolfram
authors.initials: W
authors.lastname: Schwindt
mesh_terms: D000818:Animals; D001810:Blood Volume; D001921:Brain / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004558:Electric Stimulation; D005073:Evoked Potentials, Somatosensory; D005552:Forelimb / Q000502:physiology*; D006439:Hemodynamics; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D010100:Oxygen