title: Functional NMDA receptors at axonal growth cones of young hippocampal neurons.
abstract: NMDA receptors (NMDARs) are critical to the development of the nervous system, although their roles at axonal growth cones are unclear. We examined NMDAR localization and function at axonal growth cones of young hippocampal neurons. Our immunocytochemical data showed that native and transfected NMDAR subunits are expressed in axons and growth cones of young (days in vitro 3-6) hippocampal rat neurons. Moreover, immunogold electron microscopy showed that NR1 is expressed in growth cones of postnatal day 2 rat hippocampus. Local application of NMDAR agonists to growth cones of voltage-clamped neurons evoked inward currents that were blocked by bath application of an NMDAR antagonist (dl-APV), indicating that these NMDARs are functional. In addition, calcium imaging experiments indicated that NMDARs present in growth cones mediate calcium influx. Calcium transients in growth cones persisted despite pharmacological blockade of voltage-sensitive calcium channels and depletion of intracellular calcium stores. Our findings reveal the presence of functional NMDARs in axons and growth cones of young neurons, suggesting a role for these receptors in axonal guidance and synapse formation during neuronal development.
authors.affiliation: Section on Synaptic Transmission and Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Philip Y
authors.initials: PY
authors.lastname: Wang
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Petralia
authors.forename: Ya-Xian
authors.initials: YX
authors.lastname: Wang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wenthold
authors.forename: Stephan D
authors.initials: SD
authors.lastname: Brenowitz
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D049108:Cell Enlargement; D002478:Cells, Cultured; D020439:Growth Cones / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate