The role of brain-derived neurotrophic factor receptors in the mature hippocampus: modulation of long-term potentiation through a presynaptic mechanism involving TrkB.
The neurotrophin BDNF has been shown to modulate long-term potentiation (LTP) at Schaffer collateral-CA1 hippocampal synapses. Mutants in the BDNF receptor gene trkB and antibodies to its second receptor p75NTR have been used to determine the receptors and cells involved in this response. Inhibition of p75NTR does not detectably reduce LTP or affect presynaptic function, but analyses of newly generated trkB mutants implicate TrkB. One mutant has reduced expression in a normal pattern of TrkB throughout the brain. The second mutant was created by cre-loxP-mediated removal of TrkB in CA1 pyramidal neurons of this mouse. Neither mutant detectably impacts survival or morphology of hippocampal neurons. TrkB reduction, however, affects presynaptic function and reduces the ability of tetanic stimulation to induce LTP. Postsynaptic glutamate receptors are not affected by TrkB reduction, indicating that BDNF does not modulate plasticity through postsynaptic TrkB. Consistent with this, elimination of TrkB in postsynaptic neurons does not affect LTP. Moreover, normal LTP is generated in the mutant with reduced TrkB by a depolarization-low-frequency stimulation pairing protocol that puts minimal demands on presynaptic terminal function. Thus, BDNF appears to act through TrkB presynaptically, but not postsynaptically, to modulate LTP.
Xu
B
B
Howard Hughes Medical Institute, Program in Neuroscience and Department of Physiology, University of California, San Francisco, California 94143, USA.
Gottschalk
W
W
Chow
A
A
Wilson
R I
RI
Schnell
E
E
Zang
K
K
Wang
D
D
Nicoll
R A
RA
Lu
B
B
Reichardt
L F
LF
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000235:genetics; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020800:Receptor, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020813:Receptor, trkB / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells
D000943:Antigens, Differentiation; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017470:Receptors, Glutamate; D020813:Receptor, trkB; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases