Metabotropic action of postsynaptic kainate receptors triggers hippocampal long-term potentiation

Petrović, Marina; Silva, Silvia Viana da; Clement, James P.; Vyklicky, Ladislav; Mulle, Christophe; González‐González, Inmaculada M.; Henley, Jeremy M.

doi:10.1038/nn.4505

Cited by 48 publications

(80 citation statements)

References 64 publications

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“…Therefore, mechanisms distinct from calcium permeability of the channel must contribute to PHP expression. One possibility is that DKaiR1D signals through an undefined metabotropic mechanism during PHP (Petrovic et al, 2017; Rozas et al, 2003; Rutkowska-Wlodarczyk et al, 2015), which might contribute to the ability of the calcium impermeable DKaiR1D R transgene, with reduced conductance (Li et al, 2016), to rescue PHP expression. Alternatively, an attractive possibility is that following PHP induction, glutamate released from nearby active zones may dynamically modulate the presynaptic membrane potential and/or action potential waveform to promote additional synaptic vesicle release.…”

Section: Discussionmentioning

confidence: 99%

A Presynaptic Glutamate Receptor Subunit Confers Robustness to Neurotransmission and Homeostatic Potentiation

et al. 2017

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SUMMARY Homeostatic signaling systems are thought to interface with other forms of plasticity to ensure flexible yet stable levels of neurotransmission. The role of neurotransmitter receptors in this process, beyond mediating neurotransmission itself, is not known. Through a forward genetic screen, we have identified the Drosophila kainate-type ionotropic glutamate receptor subunit DKaiR1D to be required for the retrograde, homeostatic potentiation of synaptic strength. DKaiR1D is necessary in presynaptic motor neurons, localized near active zones, and confers robustness to the calcium sensitivity of baseline synaptic transmission. Acute pharmacological blockade of DKaiR1D disrupts homeostatic plasticity, indicating that this receptor is required for the expression of this process, distinct from developmental roles. Finally, we demonstrate that calcium permeability through DKaiR1D is necessary for baseline synaptic transmission, but not for homeostatic signaling. We propose that DKaiR1D is a glutamate autoreceptor that promotes robustness to synaptic strength and plasticity with active zone specificity.

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Section: Discussionmentioning

confidence: 99%

A Presynaptic Glutamate Receptor Subunit Confers Robustness to Neurotransmission and Homeostatic Potentiation

et al. 2017

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“…Transient KAR activation can elicit a lasting upregulation of KARs at the cell surface because of increased recycling back to the surface (Martin et al., 2008, González-González and Henley, 2013), and this form of KAR activation can also induce long-term potentiation (LTP) of AMPARs (Petrovic et al., 2017, Sanjana et al., 2012). Here we show that transient kainate stimulation decreases the supply of de novo KARs through the secretory pathway.…”

Section: Discussionmentioning

confidence: 99%

Assembly, Secretory Pathway Trafficking, and Surface Delivery of Kainate Receptors Is Regulated by Neuronal Activity

et al. 2017

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SummaryIonotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity. We show that the delivery of de novo kainate receptors is differentially regulated by modulation of GluK2 Q/R editing, PKC phosphorylation, and PDZ ligand interactions. These findings reveal that, in addition to short-term regulation of iGluRs by recycling/endocytosis and long-term modulation by altered transcription/translation, the trafficking of iGluRs through the secretory pathway is under tight activity-dependent control to determine the numbers and properties of surface-expressed iGluRs.

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“…In Neto2 −/− , but not Neto1 −/− , slices, the mEPSC amplitude was lower as compared with the WT, pointing to a postsynaptic phenotype. NETO2 can target KARs to postsynaptic sites at CA1 neurons (Copits et al, 2011; Sheng et al, 2015), which might influence synaptogenesis (Marchal and Mulle, 2004; Lanore et al, 2012; Petrovic et al, 2017) via a different but complementary mechanism. In addition, NETO2 might influence synaptic maturation via KAR independent mechanisms, for example via the recently described interaction with the KCC2 (Ivakine et al, 2013) implicated in regulation of spine density (Li et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

NETO1 Guides Development of Glutamatergic Connectivity in the Hippocampus by Regulating Axonal Kainate Receptors

Orav

Atanasova

Shintyapina

et al. 2017

eNeuro

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Kainate-type glutamate receptors (KARs) are highly expressed in the developing brain, where they are tonically activated to modulate synaptic transmission, network excitability and synaptogenesis. NETO proteins are auxiliary subunits that regulate biophysical properties of KARs; however, their functions in the immature brain are not known. Here, we show that NETO1 guides the development of the rodent hippocampal CA3-CA1 circuitry via regulating axonal KARs. NETO deficiency reduced axonal targeting of most KAR subunits in hippocampal neurons in a subtype independent manner. As an interesting exception, axonal delivery of GluK1c was strongly and selectively impaired in the Neto1 −/−, but not Neto2 −/−, neurons. Correspondingly, the presynaptic GluK1 KAR activity that tonically inhibits glutamate release at immature CA3-CA1 synapses was completely lost in the absence of NETO1 but not NETO2. The deficit in axonal KARs at Neto1 −/− neurons resulted in impaired synaptogenesis and perturbed synchronization of CA3 and CA1 neuronal populations during development in vitro. Both these Neto1 −/− phenotypes were fully rescued by overexpression of GluK1c, emphasizing the role of NETO1/KAR complex in development of efferent connectivity. Together, our data uncover a novel role for NETO1 in regulation of axonal KARs and identify its physiological significance in development of the CA3-CA1 circuit.

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Metabotropic action of postsynaptic kainate receptors triggers hippocampal long-term potentiation

Abstract: 30Long-term potentiation (LTP) in the rat hippocampus is the most extensively studied cellular

Cited by 48 publications

References 64 publications

A Presynaptic Glutamate Receptor Subunit Confers Robustness to Neurotransmission and Homeostatic Potentiation

A Presynaptic Glutamate Receptor Subunit Confers Robustness to Neurotransmission and Homeostatic Potentiation

Assembly, Secretory Pathway Trafficking, and Surface Delivery of Kainate Receptors Is Regulated by Neuronal Activity

NETO1 Guides Development of Glutamatergic Connectivity in the Hippocampus by Regulating Axonal Kainate Receptors

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