BDNF acutely increases tyrosine phosphorylation of the NMDA receptor subunit 2B in cortical and hippocampal postsynaptic densities

Lin, Siang-Yo; Wu, Kuang‐Chong; Levine, Eric S.; Mount, Howard T.J.; Suen, Piin-chau; Black, Ira B.

doi:10.1016/s0169-328x(97)00349-5

Cited by 250 publications

(191 citation statements)

References 47 publications

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“…Interestingly, it has been previously shown that phosphorylation of tyrosine residues of NMDA receptor subunits enhances NMDA receptor function (Wang and Salter 1994). Consistent with this observation, TrkB activation has been shown to rapidly phosphorylate the NMDA receptor subunits NR1 and NR2B in isolated postsynaptic densities (Suen et al 1997;Lin et al 1998). With respect to NMDA receptor subunit involvement in learning and memory, restricted genetic deletion of the NR1 subunit in the CA1 region of the hippocampus using the conditional Cre/loxP recombination approach produces impaired NMDA-dependent LTP, and spatial memory (Tsien et al 1996a,b).…”

Section: Bdnf and Memory Consolidationmentioning

confidence: 59%

From Acquisition to Consolidation: On the Role of Brain-Derived Neurotrophic Factor Signaling in Hippocampal-Dependent Learning

Tyler¹,

Alonso²,

Bramham³

et al. 2002

Learn. Mem.

611

398

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One of the most rigorously investigated problems in modern neuroscience is to decipher the mechanisms by which experience-induced changes in the central nervous system are translated into behavioral acquisition, consolidation, retention, and subsequent recall of information. Brain-derived neurotrophic factor (BDNF) has recently emerged as one of the most potent molecular mediators of not only central synaptic plasticity, but also behavioral interactions between an organism and its environment. Recent experimental evidence indicates that BDNF modulates synaptic transmission and plasticity by acting across different spatial and temporal domains. BDNF signaling evokes both short-and long-term periods of enhanced synaptic physiology in both pre-and postsynaptic compartments of central synapses. Specifically, BDNF/TrkB signaling converges on the MAP kinase pathway to enhance excitatory synaptic transmission in vivo, as well as hippocampal-dependent learning in behaving animals. Emerging concepts of the intracellular signaling cascades involved in synaptic plasticity induced through environmental interactions resulting in behavioral learning further support the contention that BDNF/TrkB signaling plays a fundamental role in mediating enduring changes in central synaptic structure and function. Here we review recent literature showing the involvement of BDNF/TrkB signaling in hippocampal-dependent learning paradigms, as well as in the types of cellular plasticity proposed to underlie learning and memory.

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Section: Bdnf and Memory Consolidationmentioning

confidence: 59%

From Acquisition to Consolidation: On the Role of Brain-Derived Neurotrophic Factor Signaling in Hippocampal-Dependent Learning

Tyler¹,

Alonso²,

Bramham³

et al. 2002

Learn. Mem.

611

398

View full text Add to dashboard Cite

show abstract

“…In addition, BDNF rapidly enhances NMDA-induced currents in cultured hippocampal neurons, primarily through receptors containing NR2B subunits (Levine and Kolb, 2000). Thus, phosphorylation of NR1 and NR2B subunits by TrkB-initiated signaling cascades, as shown by Lin et al (1998), is the most likely mechanism of immediate BDNF actions on NMDAR function. It is unclear at this time whether long-term BDNF exposure as studied here has similar effects on NMDARs.…”

Section: Discussionmentioning

confidence: 98%

BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons

Pozzo-Miller

2006

Brain Research

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BDNF, a member of the neurotrophin family, is emerging as a key modulator of synaptic structure and function in the CNS. Due to the critical role of postsynaptic Ca 2+ signals in dendritic development and synaptic plasticity, we tested whether long-term exposure to BDNF affects Ca 2+ elevations evoked by coincident excitatory postsynaptic potentials (EPSPs) and back-propagating action potentials (bAPs) in spiny dendrites of CA1 pyramidal neurons within hippocampal slice cultures. In control neurons, a train of 5 coincident EPSPs and bAPs evoked Ca 2+ elevations in oblique radial branches of the main apical dendrite that were of similar amplitude than those evoked by a train of 5 bAPs alone. On the other hand, dendritic Ca 2+ signals evoked by coincident EPSPs and bAPs were always larger than those triggered by bAPs in CA1 neurons exposed to BDNF for 48 h. This difference was not observed after blockade of NMDA receptors (NMDARs) with D,L-APV, but only in BDNFtreated neurons, suggesting that Ca 2+ signals in oblique radial dendrites include a synaptic NMDARdependent component. Co-treatment with the receptor tyrosine kinase inhibitor k-252a prevented the effect of BDNF on coincident dendritic Ca 2+ signals, suggesting the involvement of neurotrophin Trk receptors. These results indicate that long-term exposure to BDNF enhances Ca 2+ signaling during coincident pre-and postsynaptic activity in small spiny dendrites of CA1 pyramidal neurons, representing a potential functional consequence of neurotrophin-mediated dendritic remodeling in developing neurons.

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“…Additional findings that high-frequency stimulation or more natural theta patterns of afferent activity upregulates BDNF expression further corroborate its role in synaptic plasticity (Gooney and Lynch, 2001;Balkowiec and Katz, 2002). Mechanisms underlying the function of BDNF in plasticity include presynaptic (Gottschalk et al, 1998;Pozzo-Miller et al, 1999;Jovanovic et al, 2000;Xu et al, 2000;Zakharenko et al, 2003;Tyler et al, 2006) or postsynaptic actions Lin et al, 1998;Di Luca et al, 2001;Kovalchuk et al, 2002) as well as coordinate pre-and postsynaptic processes (Alder et al, 2005;Gartner et al, 2006). Despite a great deal of progress on the function of BDNF in LTP, investigation of its role in associative learning has only more recently begun to be examined.…”

Section: Introductionmentioning

confidence: 85%

Coordinate action of pre- and postsynaptic brain-derived neurotrophic factor is required for AMPAR trafficking and acquisition of in vitro classical conditioning

Keifer

2008

Neuroscience

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Brain-derived neurotrophic factor (BDNF) has been implicated in mechanisms of synaptic plasticity such as long-term potentiation (LTP), but its role in associative learning remains largely unknown. In the present study, we investigated the function of BDNF and its receptor tropomyosin-related kinase B (TrkB) in an in vitro model of classical conditioning. Conditioning resulted in a significant increase in BDNF and phospho (p)-Trk expression. Bath application of antibodies directed against TrkB, but not TrkA or TrkC, abolished acquisition of conditioning, as did a receptor tyrosine kinase inhibitor K252a and an inhibitor of nitric oxide synthase 7-nitroindazole. Significantly, injections of BDNF Ab into the nerve roots of presynaptic axonal projections or postsynaptic motor neurons prevented acquisition of conditioning, suggesting that BDNF is required on both sides of the synapse for modification to occur. The presynaptic proteins synaptophysin and synapsin I were increased upon conditioning or BDNF application. Furthermore, BDNF application alone mimicked conditioning-induced synaptic insertion of GluR1 and GluR4 AMPAR subunits into synapses, which was inhibited by co-application of BDNF and K252a. Data also show that extracellular signalregulated kinase (ERK) was activated in BDNF-treated preparations. We conclude that coordinate pre-and postsynaptic actions of BDNF are required for acquisition of in vitro classical conditioning.

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BDNF acutely increases tyrosine phosphorylation of the NMDA receptor subunit 2B in cortical and hippocampal postsynaptic densities

Cited by 250 publications

References 47 publications

From Acquisition to Consolidation: On the Role of Brain-Derived Neurotrophic Factor Signaling in Hippocampal-Dependent Learning

From Acquisition to Consolidation: On the Role of Brain-Derived Neurotrophic Factor Signaling in Hippocampal-Dependent Learning

BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons

Coordinate action of pre- and postsynaptic brain-derived neurotrophic factor is required for AMPAR trafficking and acquisition of in vitro classical conditioning

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