scholarly journals Two Families of TARP Isoforms that Have Distinct Effects on the Kinetic Properties of AMPA Receptors and Synaptic Currents

Neuron ◽  
2007 ◽  
Vol 55 (6) ◽  
pp. 890-904 ◽  
Author(s):  
Chang-Hoon Cho ◽  
Fannie St-Gelais ◽  
Wei Zhang ◽  
Susumu Tomita ◽  
James R. Howe
Keyword(s):  
Ampa Receptors ◽  
Kinetic Properties ◽  
Synaptic Currents

Properties of Excitatory Synaptic Connections Mediated by the Corpus Callosum in the Developing Rat Neocortex

2001 ◽  
Vol 86 (6) ◽  
pp. 2973-2985 ◽  
Author(s):  
Sanjay S. Kumar ◽  
John R. Huguenard
Keyword(s):  
Corpus Callosum ◽  
Ampa Receptors ◽  
Pyramidal Neurons ◽  
Epileptiform Activity ◽  
Cell Voltage ◽  
Inward Rectification ◽  
Kinetic Properties ◽  
Postsynaptic Receptors ◽  
Minimal Stimulation ◽  
Stimulation Of

Despite the major role of excitatory cortico-cortical connections in mediating neocortical activities, little is known about these synapses at the cellular level. Here we have characterized the synaptic properties of long-range excitatory-to-excitatory contacts between visually identified layer V pyramidal neurons of agranular frontal cortex in callosally connected neocortical slices from postnatal day 13 to 21( P13–21) rats. Midline stimulation of the corpus callosum with a minimal stimulation paradigm evoked inward excitatory postsynaptic currents (EPSCs) with an averaged peak amplitude of 56.5 ± 5 pA under conditions of whole cell voltage clamp at −70 mV. EPSCs had fixed latencies from stimulus onset and could follow stimulus trains (1–20 Hz) without changes in kinetic properties. Bath application of 2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) abolished these responses completely, indicating that they were mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs). Evoked responses were isolated in picrotoxin to yield purely excitatory PSCs, and a low concentration of NBQX (0.1 μM) was used to partially block AMPARs and prevent epileptiform activity in the tissue. Depolarization of the recorded pyramidal neurons revealed a late, slowly decaying component that reversed at ∼0 mV and was blocked by d-2-amino-5-phosphonovaleric acid. Thus AMPA and N-methyl-d-aspartate receptors (NMDARs) coexist at callosal synapses and are likely to be activated monosynaptically. The peak amplitudes and decay time constants for EPSCs evoked using minimal stimulation (±40 mV) were similar to spontaneously occurring sEPSCs. Typical conductances associated with AMPA and NMDAR-mediated components, deduced from their respective current-voltage ( I-V) relationships, were 525 ± 168 and 966 ± 281 pS, respectively. AMPAR-mediated responses showed age-dependent changes in the rectification properties of their I-V relationships. While I-Vs from animals > P15 were linear, those in the younger (< P16) age group were inwardly rectifying. Although Ca2+ permeability in AMPARs can be correlated with inward rectification, outside-out somatic patches from younger animals were characterized by Ca2+-impermeable receptors, suggesting that somatic receptors might be functionally different from those located at synapses. While the biophysical properties of AMPAR components of callosally-evoked EPSCs were similar to those evoked by stimulation of local excitatory connections, the NMDA component displayed input-specific differences. NMDAR-mediated responses for local inputs were activated at more hyperpolarized holding potentials in contrast with those evoked by callosal stimulation. Paired stimuli used to assay presynaptic release properties showed paired-pulse depression (PPD) in animals < P16, which converted to facilitation (PPF) in older animals, suggesting a developmental transition from low probability of transmitter release to high P r at these synapses and/or alterations in the properties of the underlying postsynaptic receptors. Physiologic properties of neocortical e-e connections are thus input specific and subject to developmental changes in their postsynaptic receptors.

scholarly journals The STEP61 interactome reveals subunit-specific AMPA receptor binding and synaptic regulation

2019 ◽  
Vol 116 (16) ◽  
pp. 8028-8037 ◽  
Author(s):  
Sehoon Won ◽  
Salvatore Incontro ◽  
Yan Li ◽  
Roger A. Nicoll ◽  
Katherine W. Roche
Keyword(s):  
Ampa Receptors ◽  
Protein Tyrosine Phosphatase ◽  
Protein Phosphatase ◽  
Tyrosine Phosphatase ◽  
Hippocampal Slices ◽  
Specific Protein ◽  
Synaptic Proteins ◽  
Synaptic Currents ◽  
Synaptic Regulation ◽  
Binding Partners

Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific protein phosphatase that regulates a variety of synaptic proteins, including NMDA receptors (NAMDRs). To better understand STEP’s effect on other receptors, we used mass spectrometry to identify the STEP61 interactome. We identified a number of known interactors, but also ones including the GluA2 subunit of AMPA receptors (AMPARs). We show that STEP61 binds to the C termini of GluA2 and GluA3 as well as endogenous AMPARs in hippocampus. The synaptic expression of GluA2 and GluA3 is increased in STEP-KO mouse brain, and STEP knockdown in hippocampal slices increases AMPAR-mediated synaptic currents. Interestingly, STEP61 overexpression reduces the synaptic expression and synaptic currents of both AMPARs and NMDARs. Furthermore, STEP61 regulation of synaptic AMPARs is mediated by lysosomal degradation. Thus, we report a comprehensive list of STEP61 binding partners, including AMPARs, and reveal a central role for STEP61 in differentially organizing synaptic AMPARs and NMDARs.

Prenatal exposure to morphine alters kinetic properties of NMDA receptor-mediated synaptic currents in the hippocampus of rat offspring

Hippocampus ◽  
2000 ◽  
Vol 10 (6) ◽  
pp. 654-662 ◽  
Author(s):  
San Nan Yang ◽  
Jung-Mou Yang ◽  
Jian-Nan Wu ◽  
Yu-Hshun Kao ◽  
Wen-Ya Hsieh ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Prenatal Exposure ◽  
Kinetic Properties ◽  
Synaptic Currents ◽  
Rat Offspring

scholarly journals Clmp Regulates AMPA and Kainate Receptor Responses in the Neonatal Hippocampal CA3 and Kainate Seizure Susceptibility in Mice

2020 ◽  
Vol 12 ◽  
Author(s):  
Seil Jang ◽  
Esther Yang ◽  
Doyoun Kim ◽  
Hyun Kim ◽  
Eunjoon Kim
Keyword(s):  
Object Recognition ◽  
Fear Conditioning ◽  
Adhesion Molecules ◽  
Mossy Fiber ◽  
Synaptic Proteins ◽  
Kinetic Properties ◽  
Synapse Development ◽  
Seizure Susceptibility ◽  
Synaptic Currents ◽  
Hippocampal Ca3

Synaptic adhesion molecules regulate synapse development through trans-synaptic adhesion and assembly of diverse synaptic proteins. Many synaptic adhesion molecules positively regulate synapse development; some, however, exert negative regulation, although such cases are relatively rare. In addition, synaptic adhesion molecules regulate the amplitude of post-synaptic receptor responses, but whether adhesion molecules can regulate the kinetic properties of post-synaptic receptors remains unclear. Here we report that Clmp, a homophilic adhesion molecule of the Ig domain superfamily that is abundantly expressed in the brain, reaches peak expression at a neonatal stage (week 1) and associates with subunits of AMPA receptors (AMPARs) and kainate receptors (KARs). Clmp deletion in mice increased the frequency and amplitude of AMPAR-mediated miniature excitatory post-synaptic currents (mEPSCs) and the frequency, amplitude, and decay time constant of KAR-mediated mEPSCs in hippocampal CA3 neurons. Clmp deletion had minimal impacts on evoked excitatory synaptic currents at mossy fiber-CA3 synapses but increased extrasynaptic KAR, but not AMPAR, currents, suggesting that Clmp distinctly inhibits AMPAR and KAR responses. Behaviorally, Clmp deletion enhanced novel object recognition and susceptibility to kainate-induced seizures, without affecting contextual or auditory cued fear conditioning or pattern completion-based contextual fear conditioning. These results suggest that Clmp negatively regulates hippocampal excitatory synapse development and AMPAR and KAR responses in the neonatal hippocampal CA3 as well as object recognition and kainate seizure susceptibility in mice.

Kinetic properties of two anatomically distinct excitatory synapses in hippocampal CA3 pyramidal neurons

1991 ◽  
Vol 66 (3) ◽  
pp. 1010-1020 ◽  
Author(s):  
S. H. Williams ◽  
D. Johnston
Keyword(s):  
Time Constant ◽  
Decay Time ◽  
Rise Time ◽  
Mossy Fiber ◽  
Decay Time Constant ◽  
Kinetic Properties ◽  
Synaptic Current ◽  
Synaptic Currents ◽  
Hippocampal Ca3 ◽  
The Mean

1. We have investigated the kinetic properties of pharmacologically isolated excitatory synaptic currents in hippocampal CA3 neurons. Two distinct anatomic pathways, the commissural/associational (C/A) and the mossy fiber inputs, were compared to test the hypothesis derived from cable theory that distal inputs have slower kinetics than proximal inputs when measured at the soma. 2. Intracellular recordings were made from adult rat hippocampal slices using a single-electrode voltage clamp and low-resistance microelectrodes. A mixture of 10 microM picrotoxin and 10 microM bicuculine was used to block completely fast GABAergic inhibition. The slow inhibitory input was blocked by intracellular cesium. 3. The mean reversal potential of mossy fiber synaptic currents, -2.8 mV, was not significantly different from that of the C/A synaptic current, -1.4 mV. The mean 10-90% rise time of the mossy-fiber synaptic current [1.7 +/- 0.08 (SE) ms], however, was significantly faster than the C/A synaptic current (3.2 +/- 0.16 ms). Both mossy fiber and C/A synaptic-current decays were fit with a single exponential. The decay time constant of mossy fiber synaptic currents was also faster than that of the C/A excitatory postsynaptic current, 6.5 +/- 0.4 versus 10.1 +/- 0.8 ms. The mossy fiber synaptic current decay time constant showed little voltage dependence. 4. A modified shape index plot of synaptic current rise time versus decay time constant, normalized to membrane time constant, yielded a good linear relation for C/A synapses. A poorer correlation was observed for mossy fiber synapses. 5. Both synaptic currents could be fit by alpha functions. A representative value of alpha for the mossy fiber synapse was 295/s, and for the C/A was 172/s. 6. The rise time of the mossy fiber synaptic potential was significantly faster (5.3 ms) than the C/A (7.5 ms). The decay of both mossy fiber and C/A synaptic potentials was slower than the membrane time constant, suggesting that active currents may contribute to their falling phases. This prolongation was voltage dependent but insensitive to 2-amino-5-phosphonovaleric acid. 7. Our data provide a quantitative comparison of a proximal and a more distal synaptic input to CA3 hippocampal neurons. Distal inputs show slower kinetics than proximal synapses, as predicted. However, the voltage dependence of synaptic potential decays suggests that synaptic integration may be affected by active dendritic conductances.

64 Calcium permeability and kinetic properties of native ampa receptors

1996 ◽  
Vol 14 ◽  
pp. 66-66
Author(s):  
H. Monyer ◽  
T. Melcher ◽  
M.V. Catania ◽  
J.P. Geiger ◽  
P. Jonas
Keyword(s):  
Ampa Receptors ◽  
Kinetic Properties ◽  
Calcium Permeability

Theta-Frequency Facilitation of AMPA Receptor-Mediated Synaptic Currents in the Principal Cells of the Medial Septum

2001 ◽  
Vol 85 (4) ◽  
pp. 1709-1718 ◽  
Author(s):  
John N. Armstrong ◽  
Brian A. MacVicar
Keyword(s):  
Ampa Receptor ◽  
Ampa Receptors ◽  
Laser Scanning ◽  
Medial Septum ◽  
Laser Scanning Microscopy ◽  
Projection Neurons ◽  
Synaptic Currents ◽  
External Application ◽  
Septal Neurons ◽  
Current Facilitation

Recent evidence suggests that Ca2+-permeable AMPA receptors display rapid, short-lasting current facilitation. In this study, we investigated the properties of AMPA receptor-mediated synaptic currents in medial septal neurons of the rat in an in vitro slice preparation. Immunocytochemistry with a selective antibody to the GluR2 subunit revealed that both choline acetyltransferase-containing and parvalbumin-containing neurons of the medial septum express no detectable GluR2 subunit immunoreactivity. We used whole cell voltage-clamp recordings to measure synaptically evoked AMPA receptor-mediated currents from medial septal neurons following stimulation of midline afferents. The GYKI 52466 (50 μM)- and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) (20 μM)-sensitive AMPA receptor-mediated component of the synaptic response was isolated by blocking GABAA- and N-methyl-d-aspartate receptor-mediated currents with 30 μM bicuculline and 100 μM 2-amino-5-phosphonovaleric acid, respectively. In some cases, patched cells were filled with Lucifer yellow (0.1%) and imaged using 2-photon laser scanning microscopy. AMPA receptor-mediated currents that were observed in large medial septal neurons (20–30 μm) displayed rectification. These currents were sensitive to external application of philanthotoxin-343 (PhTx-343, 50 μM), a potent, high-affinity antagonist of Ca2+-permeable, GluR2-lacking AMPA receptors. Rectifying AMPA receptor-mediated currents also displayed a rapid increase in amplitude when evoked five times at low frequency such as 6 Hz. In contrast to currents observed in large medial septal neurons, AMPA-receptor mediated currents evoked in the remaining small (8–11 μm) neurons were nonrectifying and displayed rapid synaptic depression when stimulated five times at 6 Hz. The currents evoked in these cells were unaffected by external application of PhTx-343 and were therefore GluR2-containing AMPA receptors. The results of the present study demonstrate that the principal projection neurons of the medial septum contain PhTx-343-sensitive, GluR2-lacking AMPA receptors that display rapid current facilitation when stimulated at low frequencies.

scholarly journals Dominant negative mutant of ionotropic glutamate receptor subunit GluR3: implications for the role of a cysteine residue for its channel activity and pharmacological properties

1997 ◽  
Vol 322 (2) ◽  
pp. 385-391 ◽  
Author(s):  
Kei WATASE ◽  
Masayuki SEKIGUCHI ◽  
Taka-Aki MATSUI ◽  
Yuko TAGAWA ◽  
Keiji WADA
Keyword(s):  
Amino Acid ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Dominant Negative Mutant ◽  
Kinetic Properties ◽  
Pharmacological Properties ◽  
Negative Effects

We reported that a 33-amino-acid deletion (from tyrosine-715 to glycine-747) in a putative extracellular loop of GluR3 produced a mutant that exhibited dominant negative effects upon the functional expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors [Sekiguchi et al. (1994) J. Biol. Chem. 269, 14559–14565]. In this study, we searched for a key residue in the dominant negative effects to explore the mechanism and examined the role of the residue in the function of the AMPA receptor. We prepared 20 GluR3 mutants with amino acid substitutions within the 33-amino-acid-region, and dominant negative effects were tested electrophysiologically in Xenopus oocytes co-expressing the mutant and normal subunits. Among the mutants, only a GluR3 mutant in which an original cysteine (Cys)-722 was replaced by alanine exhibited a dominant negative effect comparable with that of the original mutant in which the entire 33-amino-acid segment is deleted. The co-expression of the Cys-722 mutant did not inhibit the translation of normal subunits in oocytes. The Cys-722 mutant formed a functional homomeric receptor with significantly higher affinity for glutamate or kainate than a homomeric GluR3 receptor. The Cys-722 mutation greatly enhanced the sensitivity of GluR3 for aniracetam, which alters kinetic properties of AMPA receptors. The kainate-induced currents in oocytes expressing the Cys-722 mutant alone showed strong inward rectification. These results suggest that the Cys-722 in GluR3 is important for dominant negative effects and plays a crucial role in the determination of pharmacological properties in AMPA receptor function.

scholarly journals Slow excitatory synaptic currents generated by AMPA receptors

2021 ◽  
Author(s):  
Niccolò P. Pampaloni ◽  
Andrew J. R. Plested
Keyword(s):  
Ampa Receptors ◽  
Synaptic Currents
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