Lamotrigine suppresses neurophysiological responses to somatosensory stimulation in the rodent.
Neurotransmitter release and voltage-gated ion channel activity in excitatory neurons are critical for understanding and interpreting neuroimaging signals. Couplings between changes in neural activity and energetic/vascular responses are assumed for interpretation of neuroimaging signals. To investigate involvement of neural events to neuroenergetic/neurovascular responses, we conducted multi-modal magnetic resonance imaging (MRI) measurements (at 7.0 T) and electrophysiological recordings (with high impedance microelectrodes) for local field potential (LFP) and spiking frequency (nu) in alpha-chloralose-anesthetized rats. The rats underwent forepaw stimulation before and after treatment of lamotrigine, a neuronal voltage-gated ion channel blocker and glutamate release inhibitor. Multi-modal MRI measurements of cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) signal were combined to estimate changes in cerebral metabolic rate of oxygen consumption (CMRo2). Lamotrigine did not appreciably affect values of nu, CBF, and CMRo2 in the resting state. After lamotrigine treatment, evoked changes in LFP and nu were attenuated, which were consistent with commensurate declines in deltaCBF and deltaCMRo2. While number of evoked BOLD-activated voxels was considerably reduced with lamotrigine, intensities of voxels in middle cortical layers were affected to a lesser degree by lamotrigine. The results suggest that lamotrigine suppresses evoked neurophysiological (i.e., neural/energetic/vascular) responses, both in terms of volume of tissue activated and degree of activation in the foci. Since lamotrigine affects evoked responses but not the basal signals, it can be suggested that glutamate release and activity of voltage-gated ion channels are essential for initiating evoked energetic/vascular responses, and thereby important for interpretation of incremental changes in neuroimaging signal.
Kida
Ikuhiro
I
Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT 06510, USA.
Smith
Arien J
AJ
Blumenfeld
Hal
H
Behar
Kevin L
KL
Hyder
Fahmeed
F
D000465:Algorithms; D000758:Anesthesia; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000502:physiology; D004558:Electric Stimulation; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005110:Extracellular Space / Q000502:physiology; D000077213:Lamotrigine; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000187:drug effects*; D014227:Triazines / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D014227:Triazines; D000077213:Lamotrigine