scholarly journals Variability of quantal NMDA to AMPA current ratio in nucleus tractus solitarii neurons

2017 ◽  
Author(s):  
Caroline Strube ◽  
Florian Gackière ◽  
Layal Saliba ◽  
Fabien Tell ◽  
Jean-Pierre Kessler

AbstractThe ratio between AMPA and NMDA receptors is a key factor governing integrative and plastic properties of excitatory glutamatergic synapses. To determine whether the respective proportions of AMPA and NMDA receptors are similar or vary across a neuron's synapse, we analyzed the variability of NMDA and AMPA currents in quantal responses recorded from neurons located in the nucleus tractus solitarii. We found that the average NMDA to AMPA current ratio strongly differed between recorded neurons and that most of the intra-neuronal current ratio variability was attributable to fluctuations in NMDA current. We next performed computer simulations with a Monte Carlo model of a glutamatergic synapse to estimate the part of AMPA and NMDA currents fluctuations induced by stochastic factors. We found that NMDA current variability mainly resulted from strong channel noise with few influence of release variations. On the contrary, partly because of the presence of subconductance states, AMPA receptor channel noise was low and AMPA current fluctuations tightly reflected changes in the amount of glutamate released. We next showed that these two factors, channel noise and fluctuations in glutamate release, were sufficient to explain the observed variability of the NMDA to AMPA current ratio in quantal events recorded from the same neuron. We therefore concluded that the proportion of AMPA and NMDA receptors was similar, or roughly similar, across synapses onto the same target cell.


2009 ◽  
Vol 101 (5) ◽  
pp. 2290-2296 ◽  
Author(s):  
Felipe Espinosa ◽  
Ege T. Kavalali

Under physiological conditions N-methyl-d-aspartate (NMDA) receptor activation requires coincidence of presynaptic glutamate release and postsynaptic depolarization due to the voltage-dependent block of these receptors by extracellular Mg2+. Therefore spontaneous neurotransmission in the absence of action potential firing is not expected to lead to significant NMDA receptor activation. Here we tested this assumption in layer IV neurons in neocortex at their resting membrane potential (approximately −67 mV). In long-duration stable recordings, we averaged a large number of miniature excitatory postsynaptic currents (mEPSCs, >100) before or after application of dl-2 amino 5-phosphonovaleric acid, a specific blocker of NMDA receptors. The difference between the two mEPSC waveforms showed that the NMDA current component comprises ∼20% of the charge transfer during an average mEPSC detected at rest. Importantly, the contribution of the NMDA component was markedly enhanced at membrane potentials expected for the depolarized up states (approximately −50 mV) that cortical neurons show during slow oscillations in vivo. In addition, partial block of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor component of the mEPSCs did not cause a significant reduction in the NMDA component, indicating that potential AMPA receptor-driven local depolarizations did not drive NMDA receptor activity at rest. Collectively these results indicate that NMDA receptors significantly contribute to signaling at rest in the absence of dendritic depolarizations or concomitant AMPA receptor activity.



2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rongkang Deng ◽  
Joseph P. Y. Kao ◽  
Patrick O. Kanold

AbstractThe development of GABAergic interneurons is important for the functional maturation of cortical circuits. After migrating into the cortex, GABAergic interneurons start to receive glutamatergic connections from cortical excitatory neurons and thus gradually become integrated into cortical circuits. These glutamatergic connections are mediated by glutamate receptors including AMPA and NMDA receptors and the ratio of AMPA to NMDA receptors decreases during development. Since previous studies have shown that retinal input can regulate the early development of connections along the visual pathway, we investigated if the maturation of glutamatergic inputs to GABAergic interneurons in the visual cortex requires retinal input. We mapped the spatial pattern of glutamatergic connections to layer 4 (L4) GABAergic interneurons in mouse visual cortex at around postnatal day (P) 16 by laser-scanning photostimulation and investigated the effect of binocular enucleations at P1/P2 on these patterns. Gad2-positive interneurons in enucleated animals showed an increased fraction of AMPAR-mediated input from L2/3 and a decreased fraction of input from L5/6. Parvalbumin-expressing (PV) interneurons showed similar changes in relative connectivity. NMDAR-only input was largely unchanged by enucleation. Our results show that retinal input sculpts the integration of interneurons into V1 circuits and suggest that the development of AMPAR- and NMDAR-only connections might be regulated differently.



1994 ◽  
Vol 72 (2) ◽  
pp. 1032-1036 ◽  
Author(s):  
M. R. Pelletier ◽  
J. J. Hablitz

1. Neocortical brain slices were prepared from rats (35–50 days of age) and maintained in vitro. Intracellular recordings were obtained from neurons in cortical layers II/III. The effect of bath application of cyclothiazide (CYZ), a potent blocker of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor desensitization, on evoked synaptic activity and passive membrane properties was investigated. 2. Bath application of CYZ did not significantly affect resting membrane potential, input resistance, or repetitive firing. CYZ increased both the amplitude and duration of evoked excitatory postsynaptic potentials (EPSPs). Polysynaptic responses were also augumented. These effects persisted after the blockade of N-methyl-D-aspartate (NMDA) receptors with D-2-amino-5-phosphonovaleric acid (D-APV). The magnitude of these effects appeared to vary directly with stimulation intensity and presumably, amount of glutamate release. 3. Epileptiform activity was induced by bath application of bicuculline methiodide. The amplitude and duration of evoked paroxysmal discharges were increased by CYZ. Similar results were seen in presence of D-APV. 4. These results indicate that CYZ has significant effects on synaptic transmission. Desensitization of non-NMDA receptors may be an important mechanism for determining the time course of EPSPs and in curtailing epileptiform responses in the rat neocortex.



2015 ◽  
Vol 1622 ◽  
pp. 22-35
Author(s):  
Chessa S. Scullin ◽  
Adrian R.B. Schiess ◽  
L. Donald Partridge


2013 ◽  
Vol 110 (1) ◽  
pp. 141-152 ◽  
Author(s):  
Gillian L. Morrison ◽  
Christine J. Fontaine ◽  
Carolyn W. Harley ◽  
Qi Yuan

cFos activation in the anterior piriform cortex (aPC) occurs in early odor preference learning in rat pups ( Roth and Sullivan 2005 ). Here we provide evidence that the pairing of odor as a conditioned stimulus and β-adrenergic activation in the aPC as an unconditioned stimulus generates early odor preference learning. β-Adrenergic blockade in the aPC prevents normal preference learning. Enhancement of aPC cAMP response element-binding protein (CREB) phosphorylation in trained hemispheres is consistent with a role for this cascade in early odor preference learning in the aPC. In vitro experiments suggested theta-burst-mediated long-term potentiation (LTP) at the lateral olfactory tract (LOT) to aPC synapse depends on N-methyl-d-aspartate (NMDA) receptors and can be significantly enhanced by β-adrenoceptor activation, which causes increased glutamate release from LOT synapses during LTP induction. NMDA receptors in aPC are also shown to be critical for the acquisition, but not expression, of odor preference learning, as would be predicted if they mediate initial β-adrenoceptor-promoted aPC plasticity. Ex vivo experiments 3 and 24 h after odor preference training reveal an enhanced LOT-aPC field excitatory postsynaptic potential (EPSP). At 3 h both presynaptic and postsynaptic potentiations support EPSP enhancement while at 24 h only postsynaptic potentiation is seen. LOT-LTP in aPC is excluded by odor preference training. Taken together with earlier work on the role of the olfactory bulb in early odor preference learning, these outcomes suggest early odor preference learning is normally supported by and requires multiple plastic changes at least at two levels of olfactory circuitry.



2010 ◽  
Vol 103 (4) ◽  
pp. 2314-2314
Author(s):  
Marco Fuenzalida ◽  
David Fernández de Sevilla ◽  
Alejandro Couve ◽  
Washington Buño


2019 ◽  
Vol 121 (5) ◽  
pp. 1822-1830 ◽  
Author(s):  
Daniela Accorsi-Mendonça ◽  
Leni G. H. Bonagamba ◽  
Benedito H. Machado

Sustained hypoxia (SH) activates chemoreceptors to produce cardiovascular and respiratory responses to bring the arterial partial pressure of O2 back to the physiological range. We evaluated the effect of SH (fraction of inspired O2 = 0.10, 24 h) on glutamatergic synaptic transmission and the interaction neuron-astrocyte in neurons of the nucleus tractus solitarii (NTS). Tractus solitarius (TS) fiber stimulation induced glutamatergic currents in neurons and astrocytes. SH increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/kainate) [−183 ± 122 pA ( n = 10) vs. −353 ± 101 pA ( n = 10)] and N-methyl-d-aspartate (NMDA) current amplitude [61 ± 10 pA ( n = 7) vs. 102 ± 37 pA ( n = 10)]. To investigate the effects of SH, we used fluoroacetate (FAC), an astrocytic inhibitor, which revealed an excitatory modulation on AMPA/kainate current and an inhibitory modulation of NMDA current in control rats. SH blunted the astrocytic modulation of AMPA [artificial cerebrospinal fluid (aCSF): −353 ± 101 pA vs. aCSF + FAC: −369 ± 76 pA ( n = 10)] and NMDA currents [aCSF: 102 ± 37 pA vs. aCSF + FAC: 108 ± 32 pA ( n = 10)]. SH increased AMPA current density [control: −6 ± 3.5 pA/pF ( n = 6) vs. SH: −20 ± 12 pA/pF ( n = 7)], suggesting changes in density, conductance, or affinity of AMPA receptors. SH produced no effect on astrocytic resting membrane potential, input resistance, and AMPA/kainate current. We conclude that SH decreased the neuron-astrocyte interaction at the NTS level, facilitating the glutamatergic transmission, which may contribute to the enhancement of cardiovascular and respiratory responses to baro- and chemoreflexes activation in SH rats. NEW & NOTEWORTHY Using an electrophysiological approach, we have shown that in nucleus tractus solitarii (NTS) from control rats, astrocytes modulate the AMPA and NMDA currents in NTS neurons, changing their excitability. Sustained hypoxia (SH) increased both glutamatergic currents in NTS neurons due to 1) a reduction in the astrocytic modulation and 2) an increase in the density of AMPA receptors. These new findings show the importance of neuron-astrocyte modulation in the excitatory synaptic transmission in NTS of control and SH rats.



2008 ◽  
Vol 28 (40) ◽  
pp. 10151-10166 ◽  
Author(s):  
D. Atasoy ◽  
M. Ertunc ◽  
K. L. Moulder ◽  
J. Blackwell ◽  
C. Chung ◽  
...  


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