Brain-derived neurotrophic factor and neurotrophin receptors modulate glutamate-induced phase shifts of the suprachiasmatic nucleus.
Light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells. Previous work raised the possibility that brain-derived neurotrophic factor (BDNF) and its high-affinity tropomyosin-related receptor kinase may be important as modulators of this excitatory input into the SCN. In order to test this possibility, we used whole-cell patch-clamp methods to measure spontaneous excitatory currents in mouse SCN neurons. We found that the amplitude and frequency of these currents were increased by BDNF and decreased by the neurotrophin receptor inhibitor K252a. The neurotrophin also increased the magnitude of currents evoked by application of N-methyl-d-aspartate and amino-methyl proprionic acid. Next, we measured the rhythms in action potential discharge from the SCN brain slice preparation. We found that application of K252a dramatically reduced the magnitude of phase shifts of the electrical activity rhythm generated by the application of glutamate. By itself, BDNF caused phase shifts that resembled those produced by glutamate and were blocked by K252a. The results demonstrate that BDNF and neurotrophin receptors can enhance glutamatergic synaptic transmission within a subset of SCN neurons and potentiate glutamate-induced phase shifts of the circadian rhythm of neural activity in the SCN.
Michel
S
S
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024-1759, USA.
Clark
J P
JP
Ding
J M
JM
Colwell
C S
CS
D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002227:Carbazoles / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D026121:Indole Alkaloids; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017470:Receptors, Glutamate / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D017470:Receptors, Glutamate; D017475:Receptors, Nerve Growth Factor; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C049985:staurosporine aglycone