Endogenous Neurotrophins Are Required for the Induction of GABAergic Long-Term Potentiation in the Neonatal Rat Hippocampus

Gubellini, Paolo

doi:10.1523/jneurosci.0824-05.2005

Cited by 67 publications

(72 citation statements)

References 32 publications

(47 reference statements)

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“…BDNF infusion appears to enhance synaptic transmission (BDNF-LTP; Messaoudi et al, 2002, see also Lu et al, 2008. Analysis of LTP in hippocampal slices further demonstrated that application of repetitive depolarizing pulses failed to induce LTP in TrkB-IgG-incubated slices, whereas TrkA and TrkC-IgG had no effect (Gubellini et al, 2005, also Korte et al, 1998. TrkB Ab application was also shown to impair LTP induced by theta-burst or paired stimulation, leaving basal synaptic transmission and shortterm plasticity intact (Kang et al, 1997).…”

Section: Role Of Bdnf In In Vitro Classical Conditioningmentioning

confidence: 89%

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: Role Of Bdnf In In Vitro Classical Conditioningmentioning

confidence: 89%

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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“…One attractive candidate is BDNF, which plays a crucial role in synaptic plasticity (Poo, 2001), in GABA A -mediated LTP (Gubellini et al, 2005), and is known to be a potent regulator of spontaneous correlated network activity at early developmental stages (Aguado et al, 2003;Carmona et al, 2006). Although several lines of evidence indicate that BDNF can be released in a calcium-dependent way by depolarization of the postsynaptic cell (Goodman et al, 1996;Lessmann et al, 2003;Magby et al, 2006;Kuczewski et al, 2008a,b), the present data do not allow identifying the presynaptic or postsynaptic site of BDNF release.…”

Section: Discussionmentioning

confidence: 99%

“…One attractive candidate is BDNF, which can be released in a calciumdependent way by depolarization of the postsynaptic cell (Goodman et al, 1996;Lessmann et al, 2003;Magby et al, 2006;Kuczewski et al, 2008b). Previous studies from the immature hippocampus have shown that BDNF is the retrograde messenger required for increasing the probability of GABA and glutamate release at GABAergic and glutamatergic synapses, respectively (Gubellini et al, 2005;Mohajerani et al, 2007). Therefore, we tested whether BDNF was able to mimic the effects of STD-LTP on MF-evoked GPSCs.…”

Section: Pairing-induced Synaptic Potentiation Requires the Activatiomentioning

confidence: 99%

At Immature Mossy-Fiber–CA3 Synapses, Correlated Presynaptic and Postsynaptic Activity Persistently Enhances GABA Release and Network Excitability via BDNF and cAMP-Dependent PKA

Sivakumaran¹,

Mohajerani²,

Cherubini³

2009

J. Neurosci.

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In the adult rat hippocampus, the axons of granule cells in the dentate gyrus, the mossy fibers (MF), form excitatory glutamatergic synapses with CA3 principal cells. In neonates, MF release into their targets mainly GABA, which at this developmental stage is depolarizing. Here we tested the hypothesis that, at immature MF-CA3 synapses, correlated presynaptic [single fiber-evoked GABA A -mediated postsynaptic potentials (GPSPs)] and postsynaptic activity (back propagating action potentials) may exert a critical control on synaptic efficacy. This form of plasticity, called spike-timing-dependent plasticity (STDP), is a Hebbian type form of learning extensively studied at the level of glutamatergic synapses. Depending on the relative timing, pairing postsynaptic spiking and single MF-GPSPs induced bidirectional changes in synaptic efficacy. In case of positive pairing, spike-timing-dependent-long-term potentiation (STD-LTP) was associated with a persistent increase in GPSP slope and in the probability of cell firing. The transduction pathway involved a rise of calcium in the postsynaptic cell and the combined activity of cAMP-dependent PKA (protein kinase A) and brain-derived neurotrophic factor (BDNF). Retrograde signaling via BDNF and presynaptic TrkB receptors led to a persistent increase in GABA release. In "presynaptically" silent neurons, the enhanced probability of GABA release induced by the pairing protocol, unsilenced these synapses. Shifting E GABA from the depolarizing to the hyperpolarizing direction with bumetanide failed to modify synaptic strength. Thus, STD-LTP of GPSPs provides a reliable way to convey information from granule cells to the CA3 associative network at a time when glutamatergic synapses are still poorly developed.

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“…In CA3 pyramidal neurons, evidence has been provided that, during a restricted period of postnatal development, long-term changes in GABAergic synaptic transmission can be induced by repetitive depolarizing pulses (25,33,34). Although in these studies the conditioning protocol used for LTP induction could have been of physiological relevance, in the present case, the persistent enhancement of glutamatergic transmission at CA3-CA1 synapses depended on a calcium rise through a voltagedependent calcium channel activated by the depolarizing action of GABA during GDPs.…”

Section: Discussionmentioning

confidence: 99%

“…4). To better assess the contribution of endogenous TrkB ligands to GDP-induced potentiation, we incubated the slices for at least 3 h with a soluble form of TrkB receptor (TrkB-IgG) engineered as an immunoadhesin to prevent TrkB activation (24,25). In slices preincubated with 1 g/ml TrkB-IgGs, the pairing procedure did not affect the frequency or amplitude of sEPSCs (mean frequency values were 0.08 Ϯ 0.03 Hz in control and 0.08 Ϯ 0.02 Hz after pairing; n ϭ 6; P Ͼ 0.5; mean amplitude values were 18.9 Ϯ 2.7 pA in control and 17.7 Ϯ 2.2 pA after pairing; P Ͼ 0.5) (Fig.…”

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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Endogenous Neurotrophins Are Required for the Induction of GABAergic Long-Term Potentiation in the Neonatal Rat Hippocampus

Cited by 67 publications

References 32 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

At Immature Mossy-Fiber–CA3 Synapses, Correlated Presynaptic and Postsynaptic Activity Persistently Enhances GABA Release and Network Excitability via BDNF and cAMP-Dependent PKA

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

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