Determinants of BDNF-induced hippocampal synaptic plasticity: role of the Trk B receptor and the kinetics of neurotrophin delivery.
The neurotrophins are a class of signaling molecules known for their growth and survival-promoting activities during neuronal development. Recent studies suggest that the neurotrophins, including brain-derived neurotrophic factor (BDNF), can also dramatically influence synaptic transmission in the adult hippocampus. The experiments described in this paper indicate that ability of BDNF to potentiate synaptic transmission in the hippocampus relies on functional Trk B receptors. Moreover, the rate at which BDNF is applied to hippocampal synapses is also a potent determinant of whether synaptic potentiation will result. Hippocampal slices perfused with BDNF at a very slow flow rate (e.g., < or = 25 ml/hr) did not show synaptic potentiation. Increasing the rate of BDNF application resulted in synaptic potentiation in which the magnitude and onset kinetics of the potentiation were determined by the rate of BDNF delivery. Immunocytochemical analysis of BDNF detected with confocal microscopy confirmed these electrophysiological observations, indicating that the penetration of BDNF into hippocampal slices is influenced dramatically by the perfusion rate.
Kang
H
H
Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Jia
L Z
LZ
Suh
K Y
KY
Tang
L
L
Schuman
E M
EM
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000493:pharmacokinetics / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D018613:Microscopy, Confocal; D009414:Nerve Growth Factors / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases