title: Reduced NMDA receptor sensitivity may underlie the resistance of subpopulations of PVN neurons to excitotoxicity.
abstract: Magnocellular neurons in the paraventricular nucleus are resistant to excitotoxic cell damage. We tested the hypothesis that a modified post-synaptic response following NMDA receptor activation may underlie this resistance. Whole-cell recordings from hypothalamic slices showed that NMDA receptor activation caused dose-dependent depolarizations in both Type I (putative magnocellular) and Type II (putative parvocellular) neurons. Type II cells, however, were an order of magnitude more sensitive (10 nM) than Type I neurons (100 nM). The depolarizations recorded in Type II cells were also significantly greater (> 35% resulting in sodium channel inactivation) than those recorded in Type I neurons. This differential sensitivity of neurons to NMDA receptor activation may explain the selective resistance of magnocellular PVN neurons to excitatory neurotoxins.
authors.affiliation: Department of Physiology, Queen's University, Kingston, ON, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Bains
authors.forename: A V
authors.initials: AV
authors.lastname: Ferguson
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000187:drug effects; D012680:Sensitivity and Specificity
chemical_list: D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate