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.

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.

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.

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.

Silent glutamatergic synapses in the mammalian brain

1999 ◽  
Vol 77 (9) ◽  
pp. 735-737 ◽  
Author(s):  
John TR Isaac ◽  
Roger A Nicoll ◽  
Robert C Malenka
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptors ◽  
Neural Activity ◽  
Long Term Potentiation ◽  
Mammalian Brain ◽  
Glutamatergic Synapses ◽  
Synaptic Localization ◽  
Term Potentiation ◽  
Ampa And Nmda Receptors

Excitatory synaptic transmission in the mammalian brain is mediated primarily by α-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors that are thought to be co-localized at individual synapses. However, recent electrophysiological and anatomical data suggest that the synaptic localization of AMPA and NMDA receptors may be independently regulated by neural activity. These data are reviewed here and the implications of these findings for the mechanisms underlying synaptic plasticity are discussed.Key words: glutamate receptor, long-term potentiation (LTP), synaptic plasticity, hippocampus, cortex.

Tufted Cell Dendrodendritic Inhibition in the Olfactory Bulb Is Dependent on NMDA Receptor Activity

2001 ◽  
Vol 85 (1) ◽  
pp. 169-173 ◽  
Author(s):  
J. M. Christie ◽  
N. E. Schoppa ◽  
G. L. Westbrook
Keyword(s):  
Nmda Receptor ◽  
Olfactory Bulb ◽  
Plexiform Layer ◽  
Cell Voltage ◽  
Mitral Cells ◽  
Postsynaptic Currents ◽  
Tufted Cells ◽  
Primary Output ◽  
Sphere Of Influence ◽  
Dendrodendritic Synapses

Mitral and tufted cells constitute the primary output cells of the olfactory bulb. While tufted cells are often considered as “displaced” mitral cells, their actual role in olfactory bulb processing has been little explored. We examined dendrodendritic inhibition between tufted cells and interneurons using whole cell voltage-clamp recording. Dendrodendritic inhibitory postsynaptic currents (IPSCs) generated by depolarizing voltage steps in tufted cells were completely blocked by the N-methyl-d-aspartate (NMDA) receptor antagonistd,l-2amino-5-phosphonopentanoic acid (d,l-AP5), whereas the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 2-3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f] quinoxaline-7-sulfonamide (NBQX) had no effect. Tufted cells in the external plexiform layer (EPL) and in the periglomerular region (PGR) showed similar behavior. These results indicate that NMDA receptor–mediated excitation of interneurons drives inhibition of tufted cells at dendrodendritic synapses as it does in mitral cells. However, the spatial extent of lateral inhibition in tufted cells was much more limited than in mitral cells. We suggest that the sphere of influence of tufted cells, while qualitatively similar to mitral cells, is centered on only one or a few glomeruli.

Enflurane Directly Depresses Glutamate AMPA and NMDA Currents in Mouse Spinal Cord Motor Neurons Independent of Actions on GABAAor Glycine Receptors

2000 ◽  
Vol 93 (4) ◽  
pp. 1075-1084 ◽  
Author(s):  
Gong Cheng ◽  
Joan J. Kendig
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Glutamate Receptors ◽  
Dorsal Horn ◽  
Motor Neurons ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Anesthetic Concentration

Background The spinal cord is an important anatomic site at which volatile agents act to prevent movement in response to a noxious stimulus. This study was designed to test the hypothesis that enflurane acts directly on motor neurons to inhibit excitatory synaptic transmission at glutamate receptors. Methods Whole-cell recordings were made in visually identified motor neurons in spinal cord slices from 1- to 4-day-old mice. Excitatory postsynaptic currents (EPSCs) or potentials (EPSPs) were evoked by electrical stimulation of the dorsal root entry area or dorsal horn. The EPSCs were isolated pharmacologically into glutamate N-methyl-d-aspartate (NMDA) receptor- and non-NMDA receptor-mediated components by using selective antagonists. Currents also were evoked by brief pulse pressure ejection of glutamate under various conditions of pharmacologic blockade. Enflurane was made up as a saturated stock solution and diluted in the superfusate; concentrations were measured using gas chromatography. Results Excitatory postsynaptic currents and EPSPs recorded from motor neurons by stimulation in the dorsal horn were mediated by glutamate receptors of both non-NMDA and NMDA subtypes. Enflurane at a general anesthetic concentration (one minimum alveolar anesthetic concentration) reversibly depressed EPSCs and EPSPs. Enflurane also depressed glutamate-evoked currents in the presence of tetrodotoxin (300 nm), showing that its actions are postsynaptic. Block of inhibitory gamma-aminobutyric acid A and glycine receptors by bicuculline (20 micrometer) or strychnine (2 micrometer) or both did not significantly reduce the effects of enflurane on glutamate-evoked currents. Enflurane also depressed glutamate-evoked currents if the inhibitory receptors were blocked and if either D,L-2-amino-5-phosphonopentanoic acid (50 micrometer) or 6-cyano-7-nitroquinoxaline-2,3-dione disodium (10 micrometer) was applied to block NMDA or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-kainate receptors respectively. Conclusions Enflurane exerts direct depressant effects on both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and NMDA glutamate currents in motor neurons. Enhancement of gamma-aminobutyric acid A and glycine inhibition is not needed for this effect. Direct depression of glutamatergic excitatory transmission by a postsynaptic action on motor neurons thus may contribute to general anesthesia as defined by immobility in response to a noxious stimulus.

Large aspiny cells in the matrix of the rat neostriatum in vitro: physiological identification, relation to the compartments and excitatory postsynaptic currents

1992 ◽  
Vol 67 (6) ◽  
pp. 1669-1682 ◽  
Author(s):  
Y. Kawaguchi
Keyword(s):  
Nmda Receptors ◽  
Spike Frequency ◽  
Linear Component ◽  
Excitatory Postsynaptic Currents ◽  
Selective Antagonist ◽  
Postsynaptic Currents ◽  
Current Pulses ◽  
Cell Recording ◽  
The Matrix

1. Large aspiny neurons (20-60 microns diam) in the neostriatum were studied in an in vitro rat slice preparation by whole-cell recording to reveal physiological identification from medium-sized spiny projection cells (10-20 microns diam), relation to the patch and matrix compartments, and excitatory synaptic inputs. Recorded cells were identified by intracellular biocytin staining. Compartmental identification was made by calbindinD28K immunohistochemistry in fixed slices. 2. Large stained neurons were morphologically heterogeneous and had aspiny or sparsely spiny dendrites and dense local axonal branches. They were located in the matrix or on the patch-matrix border. Axonal branches of the large aspiny cells were preferentially distributed in the matrix and gave off terminal boutons there. Some of the secondary dendrites arising from stem dendrites running along the border, however, crossed compartment boundaries and made fine branches in a patch. 3. Large aspiny cells had less negative resting membrane potentials and lower thresholds for spike generation than medium spiny cells. They showed longer-duration and larger-amplitude afterhyperpolarizations (AHPs) than medium spiny cells. During hyperpolarizing current pulses, apparent resistance slowly reduced, and a prominent sag was observed in the voltage record, which was absent in medium spiny cells. The large aspiny cells showed no spontaneous firing but had a tendency to fire repetitive spikes in response to depolarizing current pulses, although spike interval tended to increase in later spikes. Spike frequency of large aspiny cells increased less with current intensity than that of medium spiny cells. 4. Most large aspiny cells were considered to belong to a single physiological class, although one large aspiny cells showed shorter-duration AHPs than both most other large aspiny cells and medium spiny cells, and little spike-frequency adaptation. 5. Excitatory postsynaptic currents (EPSCs) of large aspiny cells induced by intrastriatal stimulation had two components. An early, linear component was blocked by 10 microM 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), a selective antagonist of non-N-methyl-D-aspartate (NMDA) receptors. A later component with a nonlinear current-voltage (I-V) relationship was blocked by 50 microM DL-2-amino-5-phosphonovaleric acid (DL-APV), a selective antagonist of NMDA receptors. 6. From these results, four conclusions can be drawn. 1) Most large aspiny neostriatal cells in the matrix, although they take heterogeneous shapes, belong to one physiological class with long-duration AHPs and a strong time-dependent component of anomalous rectification.(ABSTRACT TRUNCATED AT 400 WORDS)

Halothane Blocks Synaptic Excitation of Inhibitory Interneurons

1996 ◽  
Vol 85 (6) ◽  
pp. 1431-1438. ◽  
Author(s):  
Misha Perouansky ◽  
Eilon D. Kirson ◽  
Yoel Yaari
Keyword(s):  
Glutamate Receptor ◽  
Hippocampal Neurons ◽  
Feedback Inhibition ◽  
Cell Voltage ◽  
Inhibitory Interneurons ◽  
Excitatory Postsynaptic Currents ◽  
Spike Threshold ◽  
Synaptic Excitation ◽  
Postsynaptic Currents ◽  
Mouse Hippocampus

Background Activation of principal hippocampal neurons is controlled by feedforward and feedback inhibition mediated by gamma-aminobutyric acidergic interneurons. The effects of halothane on glutamate receptor-mediated synaptic excitation of inhibitory interneurons have not been reported yet. Methods The effects of halothane on glutamatergic excitatory postsynaptic currents and on spike threshold in visually identified interneurons were studied with tight-seal, whole-cell voltage- and current-clamp recordings in thin slices from adult mouse hippocampus. The excitatory postsynaptic currents were pharmacologically isolated into their N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor-mediated components using selective antagonists. Results Halothane (0.37-2.78 mM) reversibly blocked non-N-methyl-D-aspartate and N-methyl-D-aspartate excitatory postsynaptic currents in hippocampal oriens-alveus interneurons. Half-maximal inhibition was observed at similar concentrations (0.59 mM and 0.50 mM, respectively). Halothane inhibited synaptically generated action potentials at concentrations that did not elevate the spike threshold. Conclusions Halothane blocks glutamate receptor-mediated synaptic activation of inhibitory interneurons in the mouse hippocampus.

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