Corticostriatal Paired-Pulse Potentiation Produced by Voltage-Dependent Activation of NMDA Receptors and L-Type Ca2+ Channels

2002 ◽  
Vol 87 (1) ◽  
pp. 157-165 ◽  
Author(s):  
Garnik Akopian ◽  
John P. Walsh
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Ampa Receptor ◽  
Brain Slices ◽  
Cell Voltage ◽  
Excitatory Postsynaptic Currents ◽  
Paired Pulse ◽  
Stimulation Intensity ◽  
Postsynaptic Currents ◽  
Voltage Dependent

AMPA and N-methyl-d-aspartate (NMDA) receptor-mediated synaptic responses expressed differential paired-pulse plasticity when examined in the same cell using intracellular or whole cell voltage-clamp recordings. Electrical stimulation of corticostriatal afferents in brain slices bathed in artificial cerebrospinal fluid containing bicuculline produces excitatory postsynaptic potentials and excitatory postsynaptic currents (EPSCs) mediated primarily by AMPA receptors. Cell-to-cell variation existed in AMPA receptor paired-pulse plasticity, but within-cell plasticity was stable over a range of stimulation intensities. Addition of 6-cyano-7-nitroquinoxalene-2,3-dione blocked most of the synaptic response leaving behind a small AP-5-sensitive component. Increasing the stimulation intensity produced large, long-lasting NMDA receptor-mediated responses. In contrast to AMPA receptor-mediated responses, NMDA receptor responses consistently showed an increase in paired-pulse potentiation with increasing stimulation intensity. This relationship was restricted to interstimulus intervals shorter than 100 ms. Paired-pulse potentiation of NMDA receptor responses was voltage-dependent and reduced by removal of extracellular Mg2+. Block of postsynaptic L-type Ca2+ channels with nifedipine produced a voltage-dependent reduction of NMDA receptor excitatory postsynaptic currents (EPSCs) and a voltage-dependent reduction of NMDA receptor paired-pulse potentiation. These data indicate depolarization during the first NMDA receptor response causes facilitation of the second by removing voltage-dependent block of NMDA receptors by Mg2+ and by activating voltage-dependent Ca2+ channels.

scholarly journals Maturation of NMDA receptor-mediated spontaneous postsynaptic currents in the rat locus coeruleus neurons

2020 ◽  
Vol 107 (1) ◽  
pp. 18-29
Author(s):  
M Kourosh-Arami ◽  
S Hajizadeh
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Locus Coeruleus ◽  
Cell Voltage ◽  
Mammalian Brain ◽  
Glutamatergic Synapses ◽  
Excitatory Postsynaptic Currents ◽  
Postnatal Maturation ◽  
Postsynaptic Currents ◽  
Spontaneous Postsynaptic Currents

AbstractIntroductionDuring mammalian brain development, neural activity leads to maturation of glutamatergic innervations to locus coeruleus. In this study, fast excitatory postsynaptic currents mediated by N-methyl-d-aspartate (NMDA) receptors were evaluated to investigate the maturation of excitatory postsynaptic currents in locus coeruleus (LC) neurons.MethodsNMDA receptor-mediated synaptic currents in LC neurons were evaluated using whole-cell voltage-clamp recording during the primary postnatal weeks. This technique was used to calculate the optimum holding potential for NMDA receptor-mediated currents and the best frequency for detecting spontaneous excitatory postsynaptic currents (sEPSC).ResultsThe optimum holding potential for detecting NMDA receptor-mediated currents was + 40 to + 50 mV in LC neurons. The frequency, amplitude, rise time, and decay time constant of synaptic responses depended on the age of the animal and increased during postnatal maturation.ConclusionThese findings suggest that most nascent glutamatergic synapses express functional NMDA receptors in the postnatal coerulear neurons, and that the activities of the neurons in this region demonstrate an age-dependent variation.

Recruitment of GABAA inhibition in rat neocortex is limited and not NMDA dependent

1995 ◽  
Vol 74 (6) ◽  
pp. 2329-2335 ◽  
Author(s):  
D. S. Ling ◽  
L. S. Benardo
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Pyramidal Neurons ◽  
Reversal Potential ◽  
Cell Voltage ◽  
Receptor Blockade ◽  
Gamma Aminobutyric Acid ◽  
Postsynaptic Currents ◽  
Nmda Receptor Blockade ◽  
Layer V

1. The recruitment of evoked fast inhibitory postsynaptic currents (IPSCs) and excitatory postsynaptic currents (EPSCs) was examined using whole cell voltage-clamp recordings from layer V pyramidal neurons in slices of rat somatosensory cortex. Synaptic currents were evoked with graded electrical stimulation to assess the relative activation of IPSCs and EPSCs. Fast GABAA ergic IPSCs were selectively recorded by holding cells at potentials equal to EPSC reversal (approximately 0 mV). EPSCs were likewise isolated by holding cells at IPSC reversal potential (about -75 mV). 2. As stimulus intensities were increased, the magnitude of the postsynaptic currents also increased. Over the range of stimuli applied (2-10 V), EPSCs did not exhibit an upper limit. However, fast gamma-aminobutyric acid-A (GABAA-mediated IPSCs reached a maximum at intensities approximately 2 times threshold. 3. The limit on fast inhibition was unresponsive to alterations in N-methyl-D-aspartate (NMDA)-mediated excitation. Exposure to nominally magnesium-free solutions or to the NMDA antagonist 3-[(RS)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid did not affect the fast IPSC maximum. Shifts in the input-output curves for submaximal activation of IPSCs were seen, which were attributed to polysynaptic excitation. 4.Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (non-NMDA) receptors with 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) completely abolished synaptically driven, fast GABAA-mediated inhibition. These findings suggested that neocortical inhibitory cells could be driven exclusively through non-NMDA transmission. 5. By comparison, in hippocampal CA1 pyramidal neurons maximal fast inhibition was sensitive to both NMDA and non-NMDA receptor blockade. 6. The results in neocortex were corroborated by direct intracellular recordings from layer V-VI interneurons. Non-NMDA receptor blockade with CNQX prevented synaptic activation of action potentials in these cells, even during cotreatment with magnesium-free solution. 7. Together, these results suggest that recruitment of GABA(A) ergic IPSCs in neocortex is ultimately driven via glutamatergic afferents arriving at non-NMDA receptors on interneurons. Properties limiting fast inhibition would favor the propagation of enhanced excitatory activity through the neuronal network.

scholarly journals Spontaneous Synaptic Activity Is Primarily GABAergic in Vestibular Nucleus Neurons of the Chick Embryo

2003 ◽  
Vol 90 (2) ◽  
pp. 1182-1192 ◽  
Author(s):  
Mei Shao ◽  
June C. Hirsch ◽  
Christian Giaume ◽  
Kenna D. Peusner
Keyword(s):  
Glutamate Receptor ◽  
Vestibular Nucleus ◽  
Glycine Receptor ◽  
Brain Slices ◽  
Reversal Potential ◽  
Cell Voltage ◽  
Synaptic Activity ◽  
Pipette Solution ◽  
Principal Cells ◽  
Postsynaptic Currents

The principal cells of the chick tangential nucleus are vestibular nucleus neurons participating in the vestibular reflexes. In 16-day embryos, the application of glutamate receptor antagonists abolished the postsynaptic responses generated on vestibular-nerve stimulation, but spontaneous synaptic activity was largely unaffected. Here, spontaneous synaptic activity was characterized in principal cells from brain slices at E16 using whole cell voltage-clamp recordings. With KCl electrodes, the frequency of spontaneous inward currents was 3.1 Hz at –60 mV, and the reversal potential was +4 mV. Cs-gluconate pipette solution allowed the discrimination of glycine/GABAA versus glutamate receptor-mediated events according to their different reversal potentials. The ratio for spontaneous excitatory to inhibitory events was about 1:4. Seventy-four percent of the outward events were GABAA, whereas 26% were glycine receptor-mediated events. Both pre- and postsynaptic GABAB receptor effects were shown, with presynaptic GABAB receptors inhibiting 40% of spontaneous excitatory postsynaptic currents (sEPSCs) and 53% of spontaneous inhibitory postsynaptic currents (sIPSCs). With TTX, the frequency decreased ∼50% for EPSCs and 23% for IPSCs. These data indicate that the spontaneous synaptic activity recorded in the principal cells at E16 is primarily inhibitory, action potential-independent, and based on the activation of GABAA receptors that can be modulated by presynaptic GABAB receptors.

Effects of Hyposmolar Solutions on Membrane Currents of Hippocampal Interneurons and Mossy Cells In Vitro

1998 ◽  
Vol 79 (2) ◽  
pp. 1108-1112 ◽  
Author(s):  
Scott C. Baraban ◽  
Philip A. Schwartzkroin
Keyword(s):  
Voltage Clamp ◽  
Hippocampal Slices ◽  
Cell Voltage ◽  
Potassium Currents ◽  
Membrane Currents ◽  
Excitatory Postsynaptic Currents ◽  
Whole Cell ◽  
Mossy Cells ◽  
Postsynaptic Currents

Baraban, Scott C. and Philip A. Schwartzkroin. Effects of hyposmolar solutions on membrane currents of hippocampal interneurons and mossy cells in vitro. J. Neurophysiol. 79: 1108–1112, 1998. Whole cell voltage-clamp recordings in rat hippocampal slices were used to investigate the effect of changes in extracellular osmolarity on voltage-activated potassium currents. Currents were evoked from oriens/alveus (O/A) interneurons, hilar interneurons, and mossy cells. Hyposmolar external solutions produced a significant potentiation of K+ current recorded from O/A and hilar interneurons, but not from mossy cells. Hyposmolar solutions also dramatically potentiated the spontaneous excitatory postsynaptic currents recorded from mossy cells. These results suggest that hippocampal excitability can be modulated by the complex actions exerted by changes in extracellular osmolarity.

scholarly journals The NMDA-to-AMPA Ratio at Synapses Onto Layer 2/3 Pyramidal Neurons Is Conserved Across Prefrontal and Visual Cortices

2003 ◽  
Vol 90 (2) ◽  
pp. 771-779 ◽  
Author(s):  
Chaelon I. O. Myme ◽  
Ken Sugino ◽  
Gina G. Turrigiano ◽  
Sacha B. Nelson
Keyword(s):  
Ampa Receptor ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Cell Voltage ◽  
Decay Kinetics ◽  
Excitatory Transmission ◽  
Layer 2 ◽  
Medial Pfc

To better understand regulation of N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor complements across the cortex, and to investigate NMDA receptor (NMDAR)-based models of persistent activity, we compared NMDA/AMPA ratios in prefrontal (PFC) and visual cortex (VC) in rat. Whole cell voltage-clamp responses were recorded in brain slices from layer 2/3 pyramidal cells of the medial PFC and VC of rats aged p16–p21. Mixed miniature excitatory postsynaptic currents (mEPSCs) having AMPA receptor (AMPAR)- and NMDAR-mediated components were isolated in nominally 0 Mg2+ ACSF. Averaged mEPSCs were well-fit by double exponentials. No significant differences in the NMDA/AMPA ratio (PFC: 27 ± 1%; VC: 28 ± 3%), peak mEPSC amplitude (PFC: 19.1 ± 1 pA; VC: 17.5 ± 0.7 pA), NMDAR decay kinetics (PFC: 69 ± 8 ms; VC: 67 ± 6 ms), or degree of correlation between NMDAR- and AMPAR-mediated mEPSC components were found between the areas (PFC: n = 27; VC: n = 28). Recordings from older rats (p26–29) also showed no differences. EPSCs were evoked extracellularly in 2 mM Mg2+ at depolarized potentials; although the average NMDA/AMPA ratio was larger than that observed for mEPSCs, the ratio was similar in the two regions. In nominally 0 Mg2+ and in the presence of CNQX, spontaneous activation of NMDAR increased recording noise and produced a small tonic depolarization which was similar in both areas. We conclude that this basic property of excitatory transmission is conserved across PFC and VC synapses and is therefore unlikely to contribute to differences in firing patterns observed in vivo in the two regions.

Synaptic Activation of Dendritic AMPA and NMDA Receptors Generates Transient High-Frequency Firing in Substantia Nigra Dopamine Neurons In Vitro

2007 ◽  
Vol 97 (4) ◽  
pp. 2837-2850 ◽  
Author(s):  
Sarah N. Blythe ◽  
Jeremy F. Atherton ◽  
Mark D. Bevan
Keyword(s):  
Nmda Receptor ◽  
Substantia Nigra ◽  
Action Potential ◽  
Nmda Receptors ◽  
High Frequency ◽  
Brain Slices ◽  
Dopamine Neurons ◽  
Frequency Pattern ◽  
High Frequency Activity ◽  
Evoked Activity

Transient high-frequency activity of substantia nigra dopamine neurons is critical for striatal synaptic plasticity and associative learning. However, the mechanisms underlying this mode of activity are poorly understood because, in contrast to other rapidly firing neurons, high-frequency activity is not evoked by somatic current injection. Previous studies have suggested that activation of dendritic N-methyl-d-aspartate (NMDA) receptors and/or G-protein-coupled receptor (GPCR)-mediated reduction of action potential afterhyperpolarization and/or activation of cation channels underlie high-frequency activity. To address their relative contribution, transient high-frequency activity was evoked using local electrical stimulation (1 s, 10–100 Hz) in brain slices prepared from p15–p25 rats in the presence of GABA and D2 dopamine receptor antagonists. The frequency, pattern, and morphology of action potentials evoked under these conditions were similar to those observed in vivo. Evoked activity and reductions in action potential afterhyperpolarization were diminished greatly by application of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or NMDA receptor selective antagonists and abolished completely by co-application of AMPA and NMDA antagonists. In contrast, application of glutamatergic and cholinergic GPCR antagonists moderately enhanced evoked activity. Dendritic pressure-pulse application of glutamate evoked high-frequency activity that was similarly sensitive to antagonism of AMPA or NMDA receptors. Taken together, these data suggest that dendritic AMPA and NMDA receptor-mediated synaptic conductances are sufficient to generate transient high-frequency activity in substantia nigra dopamine neurons by rapidly but transiently overwhelming the conductances underlying action potential afterhyperpolarization and/or engaging postsynaptic voltage-dependent ion channels in a manner that overcomes the limiting effects of afterhyperpolarization.

scholarly journals NMDA Receptor Activation by Spontaneous Glutamatergic Neurotransmission

2009 ◽  
Vol 101 (5) ◽  
pp. 2290-2296 ◽  
Author(s):  
Felipe Espinosa ◽  
Ege T. Kavalali
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Ampa Receptor ◽  
Cortical Neurons ◽  
Glutamate Release ◽  
Receptor Activation ◽  
Receptor Activity ◽  
Resting Membrane Potential ◽  
Nmda Current ◽  
Nmda Receptor Activation

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.

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