The role of brain-derived neurotrophic factor receptors in the mature hippocampus

Modulation of long-term potentiation through a presynaptic mechanism involving trkB

Baoji Xu, Wolfram Gottschalk, Ana Chow, Rachel I. Wilson, Eric Schnell, Keling Zang, Denan Wang, Roger A. Nicoll, Bai Lu, Louis F. Reichardt

Research output: Contribution to journalArticle

306 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6888-6897
Number of pages10
JournalJournal of Neuroscience
Volume20
Issue number18
StatePublished - Sep 15 2000
Externally publishedYes

Fingerprint

trkB Receptor
Long-Term Potentiation
Hippocampus
Brain-Derived Neurotrophic Factor
Neurons
Pyramidal Cells
Presynaptic Terminals
Nerve Growth Factors
Glutamate Receptors
Synapses
Antibodies
Brain
Genes

Keywords

  • CA1
  • Conditional mutant
  • Long-term potentiation
  • Neuronal survival
  • Presynaptic
  • TrkB

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The role of brain-derived neurotrophic factor receptors in the mature hippocampus : Modulation of long-term potentiation through a presynaptic mechanism involving trkB. / Xu, Baoji; Gottschalk, Wolfram; Chow, Ana; Wilson, Rachel I.; Schnell, Eric; Zang, Keling; Wang, Denan; Nicoll, Roger A.; Lu, Bai; Reichardt, Louis F.

In: Journal of Neuroscience, Vol. 20, No. 18, 15.09.2000, p. 6888-6897.

Research output: Contribution to journalArticle

Xu, B, Gottschalk, W, Chow, A, Wilson, RI, Schnell, E, Zang, K, Wang, D, Nicoll, RA, Lu, B & Reichardt, LF 2000, 'The role of brain-derived neurotrophic factor receptors in the mature hippocampus: Modulation of long-term potentiation through a presynaptic mechanism involving trkB', Journal of Neuroscience, vol. 20, no. 18, pp. 6888-6897.
Xu, Baoji ; Gottschalk, Wolfram ; Chow, Ana ; Wilson, Rachel I. ; Schnell, Eric ; Zang, Keling ; Wang, Denan ; Nicoll, Roger A. ; Lu, Bai ; Reichardt, Louis F. / The role of brain-derived neurotrophic factor receptors in the mature hippocampus : Modulation of long-term potentiation through a presynaptic mechanism involving trkB. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 18. pp. 6888-6897.
@article{948b08e56a914378a69f95d5865bd78c,
title = "The role of brain-derived neurotrophic factor receptors in the mature hippocampus: Modulation of long-term potentiation through a presynaptic mechanism involving trkB",
abstract = "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.",
keywords = "CA1, Conditional mutant, Long-term potentiation, Neuronal survival, Presynaptic, TrkB",
author = "Baoji Xu and Wolfram Gottschalk and Ana Chow and Wilson, {Rachel I.} and Eric Schnell and Keling Zang and Denan Wang and Nicoll, {Roger A.} and Bai Lu and Reichardt, {Louis F.}",
year = "2000",
month = "9",
day = "15",
language = "English (US)",
volume = "20",
pages = "6888--6897",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "18",

}

TY - JOUR

T1 - The role of brain-derived neurotrophic factor receptors in the mature hippocampus

T2 - Modulation of long-term potentiation through a presynaptic mechanism involving trkB

AU - Xu, Baoji

AU - Gottschalk, Wolfram

AU - Chow, Ana

AU - Wilson, Rachel I.

AU - Schnell, Eric

AU - Zang, Keling

AU - Wang, Denan

AU - Nicoll, Roger A.

AU - Lu, Bai

AU - Reichardt, Louis F.

PY - 2000/9/15

Y1 - 2000/9/15

N2 - 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.

AB - 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.

KW - CA1

KW - Conditional mutant

KW - Long-term potentiation

KW - Neuronal survival

KW - Presynaptic

KW - TrkB

UR - http://www.scopus.com/inward/record.url?scp=0034666105&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034666105&partnerID=8YFLogxK

M3 - Article

VL - 20

SP - 6888

EP - 6897

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 18

ER -