Activation of D1/D5 Receptors Ameliorates Decreased Intrinsic Excitability of Hippocampal Neurons Induced by Neonatal Blockade of NMDA Receptors

2021 ◽  
Author(s):  
Ernesto Griego ◽  
Melissa Hernández‐Frausto ◽  
Luis A. Márquez ◽  
Leonardo Lara‐Valderrabano ◽  
Carolina López Rubalcava ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Hippocampal Neurons ◽  
Intrinsic Excitability

scholarly journals A role for BDNF- and NMDAR-induced lysosomal recruitment of mTORC1 in the regulation of neuronal mTORC1 activity

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Dany Khamsing ◽  
Solène Lebrun ◽  
Isabelle Fanget ◽  
Nathanaël Larochette ◽  
Christophe Tourain ◽  
...  
Keyword(s):  
Amino Acids ◽  
Nmda Receptors ◽  
Hippocampal Neurons ◽  
De Novo ◽  
Long Term Potentiation ◽  
Activation Mechanism ◽  
Functional Link ◽  
Term Potentiation ◽  
Endocytic Compartments ◽  
Mtorc1 Activation

AbstractMemory and long term potentiation require de novo protein synthesis. A key regulator of this process is mTORC1, a complex comprising the mTOR kinase. Growth factors activate mTORC1 via a pathway involving PI3-kinase, Akt, the TSC complex and the GTPase Rheb. In non-neuronal cells, translocation of mTORC1 to late endocytic compartments (LEs), where Rheb is enriched, is triggered by amino acids. However, the regulation of mTORC1 in neurons remains unclear. In mouse hippocampal neurons, we observed that BDNF and treatments activating NMDA receptors trigger a robust increase in mTORC1 activity. NMDA receptors activation induced a significant recruitment of mTOR onto lysosomes even in the absence of external amino acids, whereas mTORC1 was evenly distributed in neurons under resting conditions. NMDA receptor-induced mTOR translocation to LEs was partly dependent on the BDNF receptor TrkB, suggesting that BDNF contributes to the effect of NMDA receptors on mTORC1 translocation. In addition, the combination of Rheb overexpression and artificial mTORC1 targeting to LEs by means of a modified component of mTORC1 fused with a LE-targeting motif strongly activated mTOR. To gain spatial and temporal control over mTOR localization, we designed an optogenetic module based on light-sensitive dimerizers able to recruit mTOR on LEs. In cells expressing this optogenetic tool, mTOR was translocated to LEs upon photoactivation. In the absence of growth factor, this was not sufficient to activate mTORC1. In contrast, mTORC1 was potently activated by a combination of BDNF and photoactivation. The data demonstrate that two important triggers of synaptic plasticity, BDNF and NMDA receptors, synergistically power the two arms of the mTORC1 activation mechanism, i.e., mTORC1 translocation to LEs and Rheb activation. Moreover, they unmask a functional link between NMDA receptors and mTORC1 that could underlie the changes in the synaptic proteome associated with long-lasting changes in synaptic strength.

scholarly journals The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons

eNeuro ◽  
2017 ◽  
Vol 4 (6) ◽  
pp. ENEURO.0268-17.2017 ◽  
Author(s):  
Graciano Leal ◽  
Diogo Comprido ◽  
Pasqualino de Luca ◽  
Eduardo Morais ◽  
Luís Rodrigues ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Hippocampal Neurons ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Hnrnp K ◽  
Mrna Metabolism ◽  
Dendritic Mrna

NMDA receptors and the differential ischemic vulnerability of hippocampal neurons

2006 ◽  
Vol 23 (10) ◽  
pp. 2595-2603 ◽  
Author(s):  
Christine E. Gee ◽  
Pascal Benquet ◽  
Olivier Raineteau ◽  
Lotty Rietschin ◽  
Sebastian W. Kirbach ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Hippocampal Neurons

Glycine regulation of synaptic NMDA receptors in hippocampal neurons

1996 ◽  
Vol 76 (5) ◽  
pp. 3415-3424 ◽  
Author(s):  
K. S. Wilcox ◽  
R. M. Fitzsimonds ◽  
B. Johnson ◽  
M. A. Dichter
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Hippocampal Neurons ◽  
Time Course ◽  
Hippocampal Slices ◽  
Maximal Effect ◽  
Patch Clamp Technique ◽  
Whole Cell Patch Clamp ◽  
Dissociated Cell Culture ◽  
Cultured Hippocampal Neurons

1. Although glycine has been identified as a required coagonist with glutamate at N-methyl-D-aspartate (NMDA) receptors, the understanding of glycine's role in excitatory synaptic neurotransmission is quite limited. In the present study, we used the whole cell patch-clamp technique to examine the ability of glycine to regulate current flow through synaptic NMDA receptors at excitatory synapses between cultured hippocampal neurons and in acutely isolated hippocampal slices. 2. These studies demonstrate that the glycine modulatory site on the synaptic NMDA receptor is not saturated under baseline conditions and that increased glycine concentrations can markedly increased NMDA-receptor-mediated excitatory postsynaptic currents (EPSCs) in hippocampal neurons in both dissociated cell culture and in slice. Saturation of the maximal effect of glycine takes place at different concentrations for different cells in culture, suggesting the presence of heterogenous NMDA receptor subunit compositions. 3. Bath-applied glycine had no effect on the time course of EPSCs in either brain slice or culture, indicating that desensitization of the NMDA receptor is not prevented by glycine over the time course of an EPSC. 4. When extracellular glycine concentration is high, all miniature EPSCs recorded in the cultured hippocampal neurons contained NMDA components, indicating that segregation of non-NMDA receptors at individual synaptic boutons does not occur.

scholarly journals Regulation of intrinsic excitability in hippocampal neurons by activity-dependent modulation of the KV2.1 potassium channel

Channels ◽  
2009 ◽  
Vol 3 (1) ◽  
pp. 46-56 ◽  
Author(s):  
Durga P. Mohapatra ◽  
Hiroaki Misonou ◽  
Pan Sheng-Jun ◽  
Joshua E. Held ◽  
D. James Surmeier ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Hippocampal Neurons ◽  
Intrinsic Excitability ◽  
Activity Dependent

Both NMDA and non-NMDA receptors mediate glutamate stimulation induced cofilin rod formation in cultured hippocampal neurons

2012 ◽  
Vol 1486 ◽  
pp. 1-13 ◽  
Author(s):  
Ben Chen ◽  
Min Jiang ◽  
Mi Zhou ◽  
Lulan Chen ◽  
Xu Liu ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Hippocampal Neurons ◽  
Cultured Hippocampal Neurons

20(S)-ginsenoside Rh2, a newly identified active ingredient of ginseng, inhibits NMDA receptors in cultured rat hippocampal neurons

2006 ◽  
Vol 536 (1-2) ◽  
pp. 69-77 ◽  
Author(s):  
Eunyoung Lee ◽  
Sunoh Kim ◽  
Kwang Chul Chung ◽  
Min-Kyung Choo ◽  
Dong-Hyun Kim ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Active Ingredient ◽  
Hippocampal Neurons ◽  
Ginsenoside Rh2

scholarly journals Identification of the SNARE complex mediating the exocytosis of NMDA receptors

2016 ◽  
Vol 113 (43) ◽  
pp. 12280-12285 ◽  
Author(s):  
Yi Gu ◽  
Richard L. Huganir
Keyword(s):  
Nmda Receptors ◽  
Hippocampal Neurons ◽  
Total Internal Reflection ◽  
De Novo ◽  
Receptor Trafficking ◽  
Snare Complex ◽  
Synaptic Membranes ◽  
Rab Proteins ◽  
The Central Nervous System ◽  
The Brain

In the central nervous system, NMDA receptors mediate excitatory neurotransmissions and play important roles in synaptic plasticity. The regulation of NMDA receptor trafficking is critical for neural functions in the brain. Here, we directly visualized individual exocytic events of NMDA receptors in rat hippocampal neurons by total internal reflection fluorescence microscopy (TIRFM). We found that the constitutive exocytosis of NMDA receptors included both de novo exocytic and recycling events, which were regulated by different Rab proteins. We also identified the SNAP25–VAMP1–syntaxin4 complex mediating the constitutive exocytosis of NMDA receptors. Transient knockdown of each component of the SNARE complex interfered with surface delivery of NMDA receptors to both extrasynaptic and synaptic membranes. Our study uncovers the postsynaptic function of the SNAP25–VAMP1–syntaxin4 complex in mediating the constitutive exocytosis of NMDA receptors, suggesting that this SNARE complex is involved in excitatory synaptic transmission.

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