Developmental changes in NMDA-induced intrinsic optical signals in the hippocampal dentate gyrus of children with medically intractable seizures.
The N-methyl-D-aspartate (NMDA) receptor is one of the ionotropic glutamate receptor subtypes and exhibits a voltage-dependent blockade of its channel function by extracellular magnesium. This magnesium block is known to be absent or weak early in development and is gradually acquired while the brain matures. Interestingly, in adult patients with temporal lobe epilepsy, the magnesium block appears to be altered allowing more current to flow at a negative membrane potential. We are interested whether a similar change might be observed in children's hippocampi that have frequently been involved in medically intractable seizures. In the present study, we grouped the patients into 2 categories based on the degree of brain maturity: (I) children under the age of 2 (immature, n = 2) and (II) children over the age of 2 (mature, n = 6). Dentate gyri were imaged in real time for intrinsic optical signals with the use of a transmitted light in hippocampal slice preparations. Light transmittance (LT), which reflects a neuronal synaptic depolarization and a concomitant change in cell volume, was calculated. In the immature hippocampus, LT increased significantly in response to NMDA in the presence of extracellular magnesium. However, the mature hippocampi showed little response to NMDA unless magnesium ions were removed from the extracellular artificial cerebrospinal fluid. LT increase was also induced in response to alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA); however, there were no age-dependent differences in the AMPA induced LT increase. Differential sensitivity of the NMDA receptor to extracellular magnesium between immature and mature hippocampi suggests the probable presence of developmental regulation of magnesium block for the NMDA receptor in the human hippocampus of children with medically intractable seizures.
Isokawa
M
M
Brain Research Institute, School of Medicine, University of California, Los Angeles, CA, USA. misokawa@ucla.edu
Mathern
G W
GW
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D002470:Cell Survival; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D018891:Dentate Gyrus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008027:Light; D008274:Magnesium / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology*; D055095:Optics and Photonics; D051381:Rats; D012640:Seizures / Q000473:pathology / Q000503:physiopathology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D008274:Magnesium