NMDA Receptors Increase the Size of GABAergic Terminals and Enhance GABA Release

Fiszman, Mónica L.; Barberis, Andrea; Lu, Congyi; Fu, Zhanyan; Erdélyi, Ferenc; Szabó, Gábor; Vicini, Stefano

doi:10.1523/jneurosci.4980-04.2005

Cited by 58 publications

(67 citation statements)

References 43 publications

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“…PreNMDARs modulate synaptic transmission at many excitatory cortical synapses (Berretta and Jones, 1996;Woodhall et al, 2001;Sjöström et al, 2003;Yang et al, 2006;Corlew et al, 2007), particularly during the first 3 postnatal weeks (Fiszman et al, 2005;Mameli et al, 2005;Corlew et al, 2007). Our results demonstrate that functional, NR2B-containing PreNMDARs are present in L2/3 of S1 at P14 -P22, but are restricted to a specific subset of synapses: they are present at L4 -L2/3 excitatory synapses, but not at other synapses made by L4 cells (L4 -L4 synapses) or at other inputs onto L2/3 cells (synapses of the crosscolumnar L2/3-L2/3 projection).…”

Section: Discussionmentioning

confidence: 99%

Synapse-Specific Expression of Functional Presynaptic NMDA Receptors in Rat Somatosensory Cortex

Brasier¹,

Feldman²

2008

J. Neurosci.

140

138

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Presynaptic NMDA receptors (NMDARs) modulate release and plasticity at many glutamatergic synapses, but the specificity of their expression across synapse classes has not been examined. We found that non-postsynaptic, likely presynaptic NR2B-containing NMDARs enhanced AMPA receptor-mediated synaptic transmission at layer 4 (L4) to L2/3 (L4 -L2/3) synapses in juvenile rat barrel cortex. This modulation was apparent at room temperature when presynaptic NMDARs were activated by elevation of extracellular glutamate or application of exogenous NMDAR agonists. At near physiological temperatures, modulation of transmission by presynaptic NMDARs occurred naturally, without the need for external activation. Blockade of presynaptic NMDARs depressed unitary and extracellularly evoked EPSCs at L4 -L2/3 synapses, accompanied by increases in paired-pulse ratio and coefficient of variation, indicative of a decrease in presynaptic release probability. NMDAR agonists increased the frequency of miniature EPSCs in L2/3 neurons, without altering their amplitude or kinetics. Focal application of NMDAR antagonist revealed that the NMDARs that modulate L4 -L2/3 transmission are located in L2/3, not L4, consistent with localization on terminals or axons of L4 -L2/3 synapses, rather than on the somatodendritic compartment of presynaptic L4 neurons. In contrast, presynaptic NMDARs did not modulate L4 -L4 synapses, which originate from the same presynaptic neurons as L4 -L2/3 synapses, or cross-columnar L2/3-L2/3 horizontal projections, which synapse onto the same postsynaptic target neurons. Thus, presynaptic NMDARs selectively modulate L4 -L2/3 synapses, relative to other synapses made by the same neurons. Existence of these receptors may support specialized processing or plasticity by L4 -L2/3 synapses.

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Section: Discussionmentioning

confidence: 99%

Synapse-Specific Expression of Functional Presynaptic NMDA Receptors in Rat Somatosensory Cortex

Brasier¹,

Feldman²

2008

J. Neurosci.

140

138

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“…In addition, presynaptic actions of NMDA on interneurons have previously been demonstrated in rat cerebellar slices (Glitsch and Marty, 1999) and cultured cerebellar neurons (Fiszman et al, 2005), where chronic exposure to NMDA increased spontaneous transmitter release at GABAergic synapses by enhancing the size of GABAergic boutons along the axons of developing GABAergic interneurons. Similar presynaptic effects were reported for AMPA on interneurons in stellate cells from cerebellar slices (Bureau and Mulle, 1998).…”

Section: Nmda and Ampa Receptor Activity Scales Gabaergic Synaptic Stmentioning

confidence: 96%

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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“…The availability of transgenic mice that express eGFP driven by the GAD65 promoter (Brager et al, 2003, Lopez-Bendito et al, 2004, Galarreta et al, 2004,Fiszman et al, 2005a allows direct visualization of GABAergic interneurons and the fine features of their axonal and synaptic processes. We previously reported using these mice that in the developing cerebellum, NMDA receptors promote the maturation of GABAergic basket/stellate interneurons and their axonal terminals, and increase the frequency of spontaneous GABA release (Fiszman et al, 2005a).…”

Section: Introductionmentioning

confidence: 99%

“…We previously reported using these mice that in the developing cerebellum, NMDA receptors promote the maturation of GABAergic basket/stellate interneurons and their axonal terminals, and increase the frequency of spontaneous GABA release (Fiszman et al, 2005a). Cerebellar basket/stellate interneurons reach the molecular layer postnatally, where they are innervated by parallel fibers and establish a complex inhibitory network (Eccles et al, 1967;Palay and Chan-Palay, 1974;Mejia-Gervacio and Marty, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…Cerebellar basket/stellate interneurons reach the molecular layer postnatally, where they are innervated by parallel fibers and establish a complex inhibitory network (Eccles et al, 1967;Palay and Chan-Palay, 1974;Mejia-Gervacio and Marty, 2006). Synaptic efficacy of interneuron innervation changes with development (Pouzat and Hestrin, 1997;Bureau and Mulle, 1998), and exposure to AMPA and NMDA receptors agonists increase the occurrence of miniature spontaneous inhibitory postsynaptic currents (mIPSCs, Bureau and Mulle, 1998;Glitsch and Marty, 1999;Duguid and Smart, 2004;Huang and Bordey, 2004;Fiszman et al, 2005a).…”

Section: Introductionmentioning

confidence: 99%

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Presynaptic AMPA and kainate receptors increase the size of GABAergic terminals and enhance GABA release

et al. 2007

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SUMMARYIn the developing cerebellum, NMDA receptors promote the maturation of axonal terminals of inhibitory interneurons. We compared the effects of AMPA/kainate receptor agonists in cultured cerebellar cells from GAD65-eGFP mice. Both AMPA and kainate augmented granule cell survival without affecting interneurons. The action of kainate was blocked by an AMPA but not by a NMDA receptor antagonist, suggesting AMPA receptor involvement. AMPA and kainate increased the size of the GABAergic terminals and the action of kainate was insensitive to NMDA blockers. Whole cell recordings in granule neurons revealed that chronic treatments for 5 days with kainate as well as NMDA decreased AMPA receptors expression while interneuronal kainate receptors were depressed by kainate treatment. Acute kainate applications increased mIPSCs frequency in both granule neurons and interneurons and this effect was only partially blocked by an AMPA receptor antagonist. In contrast to what was reported for NMDA, chronic treatments with kainate induced a significant decrease of the basal mIPSCs frequency but increased the acute action of kainate on mIPSCs. Direct recordings from presynaptic GABAergic terminals suggest that AMPA and kainate receptors are present in developing GABAergic terminals and their activation affect the size of GABAergic terminals and spontaneous GABA release.

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NMDA Receptors Increase the Size of GABAergic Terminals and Enhance GABA Release

Cited by 58 publications

References 43 publications

Synapse-Specific Expression of Functional Presynaptic NMDA Receptors in Rat Somatosensory Cortex

Synapse-Specific Expression of Functional Presynaptic NMDA Receptors in Rat Somatosensory Cortex

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

Presynaptic AMPA and kainate receptors increase the size of GABAergic terminals and enhance GABA release

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