Blockade of NR2B-containing NMDA receptors prevents BDNF enhancement of glutamatergic transmission in hippocampal neurons.
Learn Mem
; 6(3): 257-66, 1999.
Article
em En
| MEDLINE
| ID: mdl-10492007
ABSTRACT
Application of brain-derived neurotrophic factor (BDNF) to hippocampal neurons has profound effects on glutamatergic synaptic transmission. Both pre- and postsynaptic actions have been identified that depend on the age and type of preparation. To understand the nature of this diversity, we have begun to examine the mechanisms of BDNF action in cultured dissociated embryonic hippocampal neurons. Whole-cell patch-clamp recording during iontophoretic application of glutamate revealed that BDNF doubled the amplitude of induced inward current. Coexposure to BDNF and the NMDA receptor antagonist AP-5 markedly reduced, but did not entirely prevent, the increase in current. Coexposure to BDNF and ifenprodil, an NR2B subunit antagonist, reproduced the response observed with AP-5, suggesting BDNF primarily enhanced activity of NR2B-containing NMDA receptors with a lesser effect on non-NMDA receptors. Protein kinase involvement was confirmed with the broad spectrum inhibitor staurosporine, which prevented the response to BDNF. PKCI19-31 and H-89, selective antagonists of PKC and PKA, had no effect on the response to BDNF, whereas autocamtide-2-related inhibitory peptide, an antagonist of CaM kinase II, reduced response magnitude by 60%. These results demonstrate the predominant role of a specific NMDA receptor subtype in BDNF modulation of hippocampal synaptic transmission.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de N-Metil-D-Aspartato
/
Transmissão Sináptica
/
Ácido Glutâmico
/
Fator Neurotrófico Derivado do Encéfalo
/
Hipocampo
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Learn Mem
Assunto da revista:
NEUROLOGIA
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos