Neurotrophin secretion from hippocampal neurons evoked by long-term-potentiation-inducing electrical stimulation patterns.
The neurotrophin (NT) brain-derived neurotrophic factor (BDNF) plays an essential role in the formation of long-term potentiation (LTP). Here, we address whether this modulation by BDNF requires its continuous presence, or whether a local increase in BDNF is necessary during a specific time period of LTP initiation. Using electrical field stimulation of primary cultures of hippocampal neurons, we demonstrate that short high-frequency bursts of stimuli that induce LTP evoke also an instantaneous secretion of BDNF. In contrast, stimuli at low frequencies, inducing long-term depression, do not enhance BDNF secretion, suggesting that BDNF is specifically present, and thus required, at the time of LTP induction. The field-stimulation-mediated BDNF secretion depends on the formation of action potentials and is induced by IP(3)-mediated Ca(2+) release from intracellular stores. Experiments, aimed at determining the sites of NT secretion that use NT6, showed similar patterns of surface labeling by field stimulation to those shown previously by high potassium.
Gärtner
Annette
A
Max Planck Institute of Neurobiology, Am Klopferspitz 18A, 82152 Martinsried, Germany. agaertner@ucl.ac.uk
Staiger
Volker
V
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004558:Electric Stimulation; D004594:Electrophysiology; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000378:metabolism*; D017774:Long-Term Potentiation; D008854:Microscopy, Electron; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D000242:Cyclic AMP; D002118:Calcium