Single-Cell Characterization of Retrograde Signaling by Brain-Derived Neurotrophic Factor

Magby, Jason P.; Bi, Cheng; Chen, Zhe-Yu; Lee, Francis S.; Plummer, Mark R.

doi:10.1523/jneurosci.4576-06.2006

Cited by 63 publications

(65 citation statements)

References 51 publications

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“…Moreover, BDNF could act on TrkB receptors localized pre-and/or postsynaptically regardless of the source of BDNF release. In our experiments, BDNF could have been released presynaptically and diffused to the postsynaptic side (Kohara et al, 2001), or postsynaptically to affect the presynaptic side (for reviews, see Tao and Poo, 2001;Magby et al, 2006). However, even if transsynaptic effects of BDNF normally occur in this preparation, functional BDNF from the opposite side of the synapse was insufficient to rescue conditioning following BDNF suppression on one side.…”

Section: Pre-and Postsynaptic Effects Of Bdnfmentioning

confidence: 84%

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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Section: Pre-and Postsynaptic Effects Of Bdnfmentioning

confidence: 84%

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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“…Our results also strengthen the recent concept that most signaling systems for axon growth and directional guidance including brain‐derived neurotrophic factor (BDNF)–tropomyosin receptor kinase B (TrkB; Song et al , 1997), Slit–Roundabout (Alpár et al , 2014; Guan et al , 2007), endocannabinoid (Berghuis et al , 2007), and semaphorin–plexin signaling (Orr et al , 2017) switch from their developmental roles to tune synaptic neurotransmission and plasticity, often via retrograde signaling, in the postnatal brain. Here, CNTF satisfies a role to enhance NE activity in the LC, alike BDNF released onto cortical interneurons (Inagaki et al , 2008; Magby et al , 2006), but does so through volume transmission in the liquor space. Then, CNTF action is specified by the expression of its cognate Trk receptor (CNTFRα) in NE neurons of the brainstem (Ip et al , 1993).…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic CNTF volume transmission shapes cortical noradrenergic excitability upon acute stress

et al. 2018

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Stress‐induced cortical alertness is maintained by a heightened excitability of noradrenergic neurons innervating, notably, the prefrontal cortex. However, neither the signaling axis linking hypothalamic activation to delayed and lasting noradrenergic excitability nor the molecular cascade gating noradrenaline synthesis is defined. Here, we show that hypothalamic corticotropin‐releasing hormone‐releasing neurons innervate ependymal cells of the 3rd ventricle to induce ciliary neurotrophic factor (CNTF) release for transport through the brain's aqueductal system. CNTF binding to its cognate receptors on norepinephrinergic neurons in the locus coeruleus then initiates sequential phosphorylation of extracellular signal‐regulated kinase 1 and tyrosine hydroxylase with the Ca2+‐sensor secretagogin ensuring activity dependence in both rodent and human brains. Both CNTF and secretagogin ablation occlude stress‐induced cortical norepinephrine synthesis, ensuing neuronal excitation and behavioral stereotypes. Cumulatively, we identify a multimodal pathway that is rate‐limited by CNTF volume transmission and poised to directly convert hypothalamic activation into long‐lasting cortical excitability following acute stress.

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“…Therefore, the postsynaptic cell provides a transcellular retrograde signal to the presynaptic neuron. One attractive candidate is BDNF, which can be released in a calcium-dependent way by depolarization of the postsynaptic cell (18)(19)(20) and plays a crucial role in synaptic plasticity (21). BDNF acts on tropomyosin-related kinase receptor B (TrkB), and this interaction activates different signaling pathways.…”

Section: Pairing-induced Synaptic Potentiation Requires the Activatiomentioning

confidence: 99%

Correlated network activity enhances synaptic efficacy via BDNF and the ERK pathway at immature CA3–CA1 connections in the hippocampus

Mohajerani

Sivakumaran²,

Zacchi³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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At early developmental stages, correlated neuronal activity is thought to exert a critical control on functional and structural refinement of synaptic connections. In the hippocampus, between postnatal day 2 (P2) and P6, network-driven giant depolarizing potentials (GDPs) are generated by the synergistic action of glutamate and GABA, which is depolarizing and excitatory. Here the rising phase of GDPs was used to trigger Schaffer collateral stimulation in such a way that synchronized network activity was coincident with presynaptic activation of afferent input. This procedure produced a persistent increase in spontaneous and evoked ␣-amino-3-hydroxy-5-methyl-4-isoxadepropionic acid-mediated glutamatergic currents, an effect that required calcium influx through postsynaptic L-type calcium channels. No potentiation was observed when a delay of 3 sec was introduced between GDPs and afferent stimulation. Pairing-induced potentiation was prevented by scavengers of endogenous BDNF or tropomyosin-related kinase receptor B (TrkB) receptor antagonists. Blocking TrkB receptors in the postsynaptic cell did not prevent the effects of pairing, suggesting that BDNF, possibly secreted from the postsynaptic cell during GDPs, acts on TrkB receptors localized on presynaptic neurons. Application of exogenous BDNF mimicked the effects of pairing on synaptic transmission. In addition, pairing-induced synaptic potentiation was blocked by ERK inhibitors, suggesting that BDNF activates the MAPK/ERK cascade, which may lead to transcriptional regulation and new protein synthesis in the postsynaptic neuron. These results support the hypothesis that, during a critical period of postnatal development, GABA A-mediated GDPs are instrumental in tuning excitatory synaptic connections and provide insights into the molecular mechanisms involved in this process.development ͉ giant depolarizing potential ͉ excitatory postsynaptic current ͉ synaptic pairing ͉ TrkB receptors S pontaneously occurring neuronal oscillations constitute a hallmark of developmental networks (1). In the immature hippocampus, giant depolarizing potentials (GDPs) represent a primordial form of synchrony between neurons, which precedes more organized forms of activity, such as the theta and gamma rhythms (2). These events, which are characterized by recurrent membrane depolarization with superimposed fast-action potentials separated by long and variable intervals of several seconds, are generated when the synaptic traffic and cell firing within the network increase to a threshold level (3). GDPs are synaptic in origin and involve the action of both glutamate and GABA, which, during a restricted period of postnatal development, is depolarizing and excitatory (4-6). The depolarizing action of GABA during GDPs results in the activation of voltagedependent calcium channels and N-methyl-D-aspartate receptors (7). GDPs also can be recorded in vivo in rat pups, in which they occur during immobility periods, sleep, and feeding (8). GDP-associated calcium waves are thought to be crucial...

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Single-Cell Characterization of Retrograde Signaling by Brain-Derived Neurotrophic Factor

Cited by 63 publications

References 51 publications

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

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

Hypothalamic CNTF volume transmission shapes cortical noradrenergic excitability upon acute stress

Correlated network activity enhances synaptic efficacy via BDNF and the ERK pathway at immature CA3–CA1 connections in the hippocampus

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