Brain-derived neurotrophic factor regulation of N-methyl-D-aspartate receptor-mediated synaptic currents in suprachiasmatic nucleus neurons.
Light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells. Previous work raises the possibility that brain-derived neurotrophic factor (BDNF) and its high-affinity receptor TrkB may be important as modulators of this excitatory input into the SCN. To test this possibility, we used whole-cell patch-clamp methods to measure excitatory currents in rat SCN neurons. These currents were evoked by electrical stimulation of the optic nerve. We found that the amplitude of the N-methyl-D-aspartate (NMDA) component of the evoked excitatory postsynaptic currents (NMDA-EPSC) was increased by application of BDNF. The neurotrophin also increased the magnitude of NMDA-evoked currents in SCN neurons. The BDNF enhancement of the NMDA-EPSC was blocked by treatment with the neurotrophin receptor antagonist K252a as well as treatment with the soluble form of the TrkB receptor engineered as an immunoadhesin (TrkB IgG). Finally, the BDNF enhancement was lost in brain slices treated with the NR2B antagonist ifenprodil. The results demonstrate that BDNF and TrkB receptors are important regulators of retinal glutamatergic synaptic transmission within the SCN.
Kim
Y I
YI
Department of Physiology, Korea University College of Medicine, Seoul, Republic of Korea. yikim@korea.ac.kr
Choi
H-J
HJ
Colwell
C S
CS
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D009900:Optic Nerve / Q000502:physiology / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000276:immunology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000166:cytology*
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007074:Immunoglobulin G; D026121:Indole Alkaloids; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; C049985:staurosporine aglycone; D020813:Receptor, trkB; C010739:ifenprodil