Regulated Release and Polarized Localization of Brain-Derived Neurotrophic Factor in Hippocampal Neurons

Goodman, Lionel; Valverde, Janet; Lim, Filip; Geschwind, Michael D.; Federoff, Howard J.; Geller, Alfred I.; Hefti, Franz

doi:10.1006/mcne.1996.0017

Cited by 304 publications

(232 citation statements)

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“…BDNF expression is induced by neuronal activity (Lindholm et al, 1994;Berninger et al, 1995), and seizure activity causes a rapid increase in BDNF mRNA levels in the hippocampus and cortex (Isackson et al, 1991). BDNF is also released in an activity-dependent manner (Wetmore et al, 1994;Goodman et al, 1996). In addition, neural activity affects TrkB-mediated signaling (Poo, 2001), in part by elevating TrkB receptors on the cell surface (Du et al, 2000).…”

Section: Bdnf Modulates the Activity-dependent Scaling Of Gabaergic Smentioning

confidence: 99%

Activity-dependent scaling of GABAergic synapse strength is regulated by brain-derived neurotrophic factor

Swanwick

Murthy

Kapur

2006

Molecular and Cellular Neuroscience

100

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The homeostatic plasticity hypothesis suggests that neuronal activity scales synaptic strength. This study analyzed effects of activity deprivation on GABAergic synapses in cultured hippocampal neurons using patch clamp electrophysiology to record mIPSCs and immunocytochemistry to visualize presynaptic GAD-65 and the γ2 subunit of the GABA A receptor. When neural activity was blocked for 48 h with tetrodotoxin (TTX, 1 μM), the amplitude of mIPSCs was reduced, corresponding with diminished sizes of GAD-65 puncta and γ2 clusters. Treatment with the NMDA receptor antagonist APV (50 μM) or the AMPA receptor antagonist DNQX (20 μM) mimicked these effects, and co-application of brain-derived neurotrophic factor (BDNF, 100 ng/mL) overcame them. Moreover, when neurons were treated with BDNF alone for 48 h, these effects were reversed via the TrkB receptor. Overall, these results suggest that activity-dependent scaling of inhibitory synaptic strength can be modulated by BDNF/TrkB-mediated signaling.

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Section: Bdnf Modulates the Activity-dependent Scaling Of Gabaergic Smentioning

confidence: 99%

Activity-dependent scaling of GABAergic synapse strength is regulated by brain-derived neurotrophic factor

Swanwick

Murthy

Kapur

2006

Molecular and Cellular Neuroscience

100

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“…In this respect, it is difficult to regard NT-3 as a signal that is secreted activity dependently, which triggers neural plasticity. BDNF seems to be a more promising candidate for the signal because of its mRNA upregulation (Falkenberg et al, 1992;Patterson et al, 1992;Rocamora et al, 1992;Kokaia et al, 1993) and secretion by neuronal activity (Griesbeck et al, 1995;Goodmann et al, 1996). Generally, expression of NT-3 is highest in immature CNS and dramatically decreases with maturation.…”

Section: Inhibition Of Gaba a Receptor-mediated Ipscs By Bdnfmentioning

confidence: 99%

“…These observations suggest that in the adult CNS dynamic change in BDNF level still can trigger neuronal plasticity via activation of TrkB. Indeed, neurotrophins are secreted by neurons in both a constitutive and an activity-dependent manner Thoenen, 1995, 1996;Griesbeck et al, 1995;Thoenen, 1995;Goodmann et al, 1996). Additionally, BDNF induces long-lasting enhancement of synaptic transmission (Kang and Schuman, 1995) and facilitates the induction of long-term potentiation (LTP) in the hippocampus (Figurov et al, 1996); however, the site and mechanism of action of BDNF remain unclear, because the effect of BDNF on synaptic transmission has been assessed by analyzing field (extracellular) potential changes in most cases.…”

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confidence: 99%

Inhibition of GABA_ASynaptic Responses by Brain-Derived Neurotrophic Factor (BDNF) in Rat Hippocampus

1997

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Brain-derived neurotrophic factor (BDNF) is one of neurotrophins involved in the development and maintenance of both the peripheral nervous system and CNS. Although the expression of BDNF and its receptor TrkB still occurs in the adult stage, their physiological role in the mature CNS is not fully understood. In the present study we examined in detail the possibility that BDNF modulates synaptic neurotransmissions by using patch-clamp technique in rat hippocampal CA1 region. BDNF (20 -100 ng/ml) did not show any appreciable effect on evoked EPSCs, but it markedly reduced both evoked and spontaneous IPSCs within 5 min, and the reduction persisted while BDNF was present. BDNF also attenuated GABA A receptor-mediated response to applied GABA. However, BDNF failed to attenuate IPSCs when the postsynaptic pyramidal neuron was loaded intracellularly with 200 nM K252a, an alkaloid that inhibits the kinase activity of Trk receptor family, through the patch pipette. Intracellular application of 200 nM K252b, a weaker inhibitor of Trk-type kinase, did not affect the inhibition. The attenuating effect also was prevented by postsynaptic injection of U73122 (5 M), a broad-spectrum PLC inhibitor, and by strong chelation of intracellular Ca 2ϩ with 10 mM BAPTA. These data suggest that BDNF modulates GABA A synaptic responses by postsynaptic activation of Trk-type receptor and subsequent Ca 2ϩ mobilization in the CNS.Key words: BDNF; GABA A receptor; disinhibition; plasticity; LTP; hippocampus Brain-derived neurotrophic factor (BDNF) is one of the neurotrophins involved in the development and maintenance of both the peripheral nervous system and CNS. During brain development neurotrophins and their receptors display distinct stage-and tissue-specific patterns of expression (Ernfors et al., 1990a;Phillips et al., 1990;Merlio et al., 1992). BDNF mRNA is observed in the embryonic stage and is still present in the postnatal and adult stages (Ernfors et al., 1990b;Maisonpierre et al., 1990; Freidman et al., 1991). In the adult stage its expression level is modulated dramatically by neuronal activity (Falkenberg et al., 1992;Patterson et al., 1992;Rocamora et al., 1992;Bengzon et al., 1993;Kokaia et al., 1993). Moreover, expression of TrkB, a functional BDNF receptor, not only increases during embryonic development but also continues to increase until several weeks after birth in the hippocampus (Masana et al., 1993;Ringstedt et al., 1993). These observations suggest that in the adult CNS dynamic change in BDNF level still can trigger neuronal plasticity via activation of TrkB. Indeed, neurotrophins are secreted by neurons in both a constitutive and an activity-dependent manner Thoenen, 1995, 1996;Griesbeck et al., 1995;Thoenen, 1995;Goodmann et al., 1996). Additionally, BDNF induces long-lasting enhancement of synaptic transmission (Kang and Schuman, 1995) and facilitates the induction of long-term potentiation (LTP) in the hippocampus (Figurov et al., 1996); however, the site and mechanism of action of BDNF remain unclear, becau...

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“…Most information about BDNF release from hippocampal neurons has been derived from studies using adenoviral gene-transfer techniques to overexpress BDNF to high concentrations (Goodman et al, 1996;Griesbeck et al, 1999;Gärtner and Staiger, 2002), or cells transfected with BDNF-green fluorescent protein (GFP) expression plasmids (Hartmann et al, 2001;Kohara et al, 2001). It is unclear, however, whether mechanisms governing sorting and release of BDNF in these artificial systems are the same or different from those governing sorting and release of native BDNF (Fawcett et al, 1997).…”

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confidence: 99%

“…It is unclear, however, whether mechanisms governing sorting and release of BDNF in these artificial systems are the same or different from those governing sorting and release of native BDNF (Fawcett et al, 1997). In addition, most previous studies of BDNF release used continuous membrane depolarization to model neuronal activity (Goodman et al, 1996;Griesbeck et al, 1999). However, we showed previously, using primary sensory neurons, that patterned electrical stimulation, which more closely mimics neuronal activity in vivo, is much more effective at releasing native BDNF than continuous KCl depolarization (Balkowiec and Katz, 2000).…”

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confidence: 99%

Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons

2002

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Brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent modifications of neuronal connectivity and synaptic strength, including establishment of hippocampal long-term potentiation (LTP). To shed light on mechanisms underlying BDNF-dependent synaptic plasticity, the present study was undertaken to characterize release of native BDNF from newborn rat hippocampal neurons in response to physiologically relevant patterns of electrical field stimulation in culture, including tonic stimulation at 5 Hz, bursting stimulation at 25 and 100 Hz, and theta-burst stimulation (TBS). Release was measured using the ELISA in situ technique, developed in our laboratory to quantify secretion of native BDNF without the need to first overexpress the protein to nonphysiological levels. Each stimulation protocol resulted in a significant increase in BDNF release that was tetrodotoxin sensitive and occurred in the absence of glutamate receptor activation. However, 100 Hz tetanus and TBS, stimulus patterns that are most effective in inducing hippocampal LTP, were significantly more effective in releasing native BDNF than lower-frequency stimulation. For all stimulation protocols tested, removal of extracellular calcium, or blockade of N-type calcium channels, prevented BDNF release. Similarly, depletion of intracellular calcium stores with thapsigargin and treatment with dantrolene, an inhibitor of calcium release from caffeine-ryanodine-sensitive stores, markedly inhibited activity-dependent BDNF release. Our results indicate that BDNF release can encode temporal features of hippocampal neuronal activity. The dual requirement for calcium influx through N-type calcium channels and calcium mobilization from intracellular stores strongly implicates a role for calcium-induced calcium release in activity-dependent BDNF secretion.

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Regulated Release and Polarized Localization of Brain-Derived Neurotrophic Factor in Hippocampal Neurons

Cited by 304 publications

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Activity-dependent scaling of GABAergic synapse strength is regulated by brain-derived neurotrophic factor

Activity-dependent scaling of GABAergic synapse strength is regulated by brain-derived neurotrophic factor

Inhibition of GABA_ASynaptic Responses by Brain-Derived Neurotrophic Factor (BDNF) in Rat Hippocampus

Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons

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Regulated Release and Polarized Localization of Brain-Derived Neurotrophic Factor in Hippocampal Neurons

Cited by 304 publications

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Activity-dependent scaling of GABAergic synapse strength is regulated by brain-derived neurotrophic factor

Activity-dependent scaling of GABAergic synapse strength is regulated by brain-derived neurotrophic factor

Inhibition of GABAASynaptic Responses by Brain-Derived Neurotrophic Factor (BDNF) in Rat Hippocampus

Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons

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Inhibition of GABA_ASynaptic Responses by Brain-Derived Neurotrophic Factor (BDNF) in Rat Hippocampus