NT-3 regulates BDNF-induced modulation of synaptic transmission in cultured hippocampal neurons

Paul, Jennifer S.; Gottmann, Kurt; Leßmann, Volkmar

doi:10.1097/00001756-200108280-00010

Cited by 33 publications

(20 citation statements)

References 23 publications

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“…These results are consistent with previous findings that NT3 potentiates neuronal activity by downregulating GABAergic synaptic transmission in dissociated cortical neurons (Kim et al, 1994). In addition, Paul et al (2001) have shown that NT3 attenuates the BDNF-induced increase in EPSCs and IPSCs and c-fos expression in dissociated cultures of hippocampal neurons. NT3 is produced and released by embryonic hippocampal neurons as well as astrocytes (Rudge et al, 1992;Blondel et al, 2000;Wu et al, 2004), but the relevant source of NT3 for modulating GABA A Rs in neuron-astrocyte cocultures remains to be determined.…”

Section: Discussionsupporting

confidence: 93%

Astrocytes Regulate Inhibitory Synapse Formation via Trk-Mediated Modulation of Postsynaptic GABA_AReceptors

Elmariah¹,

Oh²,

Hughes³

et al. 2005

J. Neurosci.

161

133

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Astrocytes promote the formation and function of excitatory synapses in the CNS. However, whether and how astrocytes modulate inhibitory synaptogenesis are essentially unknown. We asked whether astrocytes regulate the formation of inhibitory synapses between hippocampal neurons during maturation in vitro. Neuronal coculture with astrocytes or treatment with astrocyte-conditioned medium (ACM) increased the number of inhibitory presynaptic terminals, the frequency of miniature IPSCs, and the number and synaptic localization of GABA A receptor (GABA A R) clusters during the first 10 d in vitro. We asked whether neurotrophins, which are potent modulators of inhibitory synaptic structure and function, mediate the effects of astrocytes on inhibitory synapses. ACM from BDNF-or tyrosine receptor kinase B (TrkB)-deficient astrocytes increased inhibitory presynaptic terminals and postsynaptic GABA A R clusters in wild-type neurons, suggesting that BDNF and TrkB expression in astrocytes is not required for these effects. In contrast, although the increase in the number of inhibitory presynaptic terminals persisted, no increase was observed in postsynaptic GABA A R clusters after ACM treatment of hippocampal neurons lacking BDNF or TrkB. These results suggest that neurons, not astrocytes, are the relevant source of BDNF and are the site of TrkB activation required for postsynaptic GABA A R modulation. These data also suggest that astrocytes may modulate postsynaptic development indirectly by stimulating Trk signaling between neurons. Together, these data show that astrocytes modulate inhibitory synapse formation via distinct presynaptic and postsynaptic mechanisms.

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Section: Discussionsupporting

confidence: 93%

Astrocytes Regulate Inhibitory Synapse Formation via Trk-Mediated Modulation of Postsynaptic GABA_AReceptors

Elmariah¹,

Oh²,

Hughes³

et al. 2005

J. Neurosci.

161

133

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“…Moreover, BDNF is also well known to affect the cell-wide homeostatic regulation of miniature synaptic currents. Chronic BDNF application has been shown to enhance both the frequency (Collin et al 2001;Paul et al 2001;Vicario-Abejon et al 1998) and the amplitude of AMPA mEPSCs (McLean Bolton et al 2000) in primary cultured hippocampal neurons. In addition, effects of BDNF on AMPA mEPSC amplitudes have been shown to be strongly dependent on the neuronal cell type investigated with opposing effects occurring in neocortical pyramidal cells as compared with GABAergic interneurons (Leslie et al 2001;Rutherford et al 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, neurotrophic factors, e.g., brain-derived neurotrophic factor (BDNF), induce long-term synaptic plasticity at cortical glutamatergic synapses (Lessmann et al 1994;Lessmann 1998;Lu 2003;Lu and Chow 1999). Both, an involvement in the input-specific potentiation of postsynaptic currents evoked by action potentials (Korte et al 1995;Patterson et al 1996) and in the cell-wide regulation of spontaneous miniature postsynaptic currents (Collin et al 2001;McLean Bolton et al 2000;Paul et al 2001;Rutherford et al 1998;Vicario-Abejon et al 1998) have been described.…”

Section: Introductionmentioning

confidence: 99%

Activity- and BDNF-Induced Plasticity of Miniature Synaptic Currents in ES Cell-Derived Neurons Integrated in a Neocortical Network

Copi¹,

Jüngling²,

Gottmann³

2005

Journal of Neurophysiology

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Copi, Andrea, Kay Jü ngling, and Kurt Gottmann. Activity-and BDNF-induced plasticity of miniature synaptic currents in ES cellderived neurons integrated in a neocortical network. J Neurophysiol 94: 4538 -4543, 2005; doi:10.1152/jn.00155.2005. In vitro differentiated embryonic stem (ES) cells have been proposed as potential donor cells for cell replacement therapies of neurodegenerative diseases. The functional synaptic integration of such cells appears conceivable because ES cell-derived neurons are well known to establish excitatory and inhibitory synapses. However, long-term synaptic plasticity, a prerequisite of memory formation, has not yet been demonstrated at these synapses. After in vitro differentiation and purification by immunoisolation, we co-cultured ES cell-derived neurons with neocortical explants, which strongly innervated the ES cell-derived target neurons. ES cell-derived neurons exhibited action potential firing similar to primary cultured neocortical neurons. The formation of glutamatergic synapses was indicated by AMPA receptor-mediated miniature excitatory postsynaptic currents (AMPA mEPSCs). In addition, a N-methyl-D-aspartate receptor-mediated, D-2-amino-5-phosphonopentanoic acid-sensitive mEPSC component was observed. We first studied activity-dependent homeostatic plasticity (synaptic scaling) of mEPSCs at glutamatergic synapses. Chronic blockade of action potential activity by TTX resulted in an increase in the amplitudes of AMPA mEPSCs. This indicates that ES cell-derived neurons are capable of a homeostatic regulation of postsynaptic AMPA receptors. In addition, we investigated neurotrophin-induced synaptic plasticity of mEPSCs at glutamatergic synapses. Chronic addition of brain-derived neurotrophic factor (BDNF; 100 ng/ml) to the culture medium resulted in an increase in both the frequency and the amplitudes of AMPA mEPSCs. These results suggest that BDNF induces the formation and/or the functional maturation of presynaptic release sites in parallel with an upregulation of postsynaptic AMPA receptors. Thus BDNF represents a potential co-factor that could improve functional synaptic integration of ES cell-derived neurons into neocortical networks.

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“…BDNF gene transcription is suppressed by DNA methylation, and this is reversed by histone acethylase which is restored by antidepressant drugs (50). NT3 deficiency caused defects both in differentiation of neuronal precursor cells and in spatial learning tasks (51), while NT3 increased the expression of BDNF (52) and modulated BDNF-induced signaling in differentiating hippocampal neurons (53). Also, NT3 was downregulated with NGF by exposure to chronic stress (54).…”

Section: Neurotrophic Factors Affecting Adult Hippocampal Neurogenesimentioning

confidence: 99%

Adult hippocampal neurogenesis and related neurotrophic factors

Lee¹,

Son²

2009

BMB Reports

202

126

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New neurons are continually generated in the subgranular zone of the dentate gyrus and in the subventricular zone of the lateral ventricles of the adult brain. These neurons proliferate, differentiate, and become integrated into neuronal circuits, but how they are involved in brain function remains unknown. A deficit of adult hippocampal neurogenesis leads to defective spatial learning and memory, and the hippocampi in neuropsychiatric diseases show altered neurogenic patterns. Adult hippocampal neurogenesis is not only affected by external stimuli but also regulated by internal growth factors including BDNF, VEGF and IGF-1. These factors are implicated in a broad spectrum of pathophysiological changes in the human brain. Elucidation of the roles of such neurotropic factors should provide insight into how adult hippocampal neurogenesis is related to psychiatric disease and synaptic plasticity.

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NT-3 regulates BDNF-induced modulation of synaptic transmission in cultured hippocampal neurons

Cited by 33 publications

References 23 publications

Astrocytes Regulate Inhibitory Synapse Formation via Trk-Mediated Modulation of Postsynaptic GABA_AReceptors

Astrocytes Regulate Inhibitory Synapse Formation via Trk-Mediated Modulation of Postsynaptic GABA_AReceptors

Activity- and BDNF-Induced Plasticity of Miniature Synaptic Currents in ES Cell-Derived Neurons Integrated in a Neocortical Network

Adult hippocampal neurogenesis and related neurotrophic factors

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NT-3 regulates BDNF-induced modulation of synaptic transmission in cultured hippocampal neurons

Cited by 33 publications

References 23 publications

Astrocytes Regulate Inhibitory Synapse Formation via Trk-Mediated Modulation of Postsynaptic GABAAReceptors

Astrocytes Regulate Inhibitory Synapse Formation via Trk-Mediated Modulation of Postsynaptic GABAAReceptors

Activity- and BDNF-Induced Plasticity of Miniature Synaptic Currents in ES Cell-Derived Neurons Integrated in a Neocortical Network

Adult hippocampal neurogenesis and related neurotrophic factors

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Astrocytes Regulate Inhibitory Synapse Formation via Trk-Mediated Modulation of Postsynaptic GABA_AReceptors

Astrocytes Regulate Inhibitory Synapse Formation via Trk-Mediated Modulation of Postsynaptic GABA_AReceptors