Neuropeptide Y2 receptors inhibit the frequency of spontaneous but not miniature EPSCs in CA3 pyramidal cells of rat hippocampus

1996 ◽  
Vol 76 (5) ◽  
pp. 3159-3168 ◽  
Author(s):  
A. R. McQuiston ◽  
W. F. Colmers
Keyword(s):  
Glutamate Release ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Receptor Activation ◽  
Rat Hippocampus ◽  
Excitatory Postsynaptic Currents ◽  
Synaptic Excitation ◽  
Postsynaptic Currents ◽  
Y2 Receptor ◽  
Ca3 Pyramidal Cells

1. Neuropeptide Y (NPY) inhibits synaptic excitation in hippocampal area CA3. We studied its site of action with the use of whole cell patch-clamp recordings from CA3 pyramidal cells of rat hippocampal slices in vitro. 2. Spontaneous excitatory postsynaptic currents (sEPSCs) were isolated with picrotoxin, to block gamma-aminobutyric acid-A receptors, whereas miniature excitatory postsynaptic currents (mEPSCs) were isolated by additionally treating the slice with tetrodotoxin (TTX) and/or Cd2+, sEPSCs and mEPSCs were eliminated by the excitatory amino acid antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) and DL-2-amino-5-phosphonovaleric acid (50 microM), and were thus solely attributable to glutamate release. 3. The interval and amplitude distributions of sEPSCS and (TTX-isolated) mEPSCS were analyzed. Either NPY or the rapidly reversible, Y2-receptor-selective agonist [6-aminohexanoic5-24] NPY, ([ahx5-24]NPY) sharply increased the inter-sEPSC intervals in 16 of 16 neurons tested. In 11 of these cells, these agonists also simultaneously shifted the sEPSC amplitude distribution to somewhat smaller amplitudes, whereas in the remaining 5 cells, no concurrent effect on amplitudes was observed. By contrast, in 15 separate neurons treated with 1 microM TTX, neither NPY nor [ahx5-24]NPY altered either mEPSC amplitude or interval distributions of the mEPSCs. 4. To directly compare the effects of Y2 receptor activation on sEPSC and mEPSC properties, we applied [ahx5-24]NPY to the same cell in the absence and presence of TTX (n = 7). sEPSC intervals were characteristically increased by the Y2 agonist in all cells; in six of seven cells the sEPSC distribution was also shifted to smaller amplitudes. TTX application reduced the mean amplitude of the synaptic events more than did [ahx5-24]NPY, while increasing their intervals. [ahx5-24]NPY had no effect in TTX. 5. NPY, acting on a Y2 receptor, inhibits impulse-dependent synaptic excitation of CA3 pyramidal cells of the rat hippocampus by an entirely presynaptic action.

Large Amplitude Miniature Excitatory Postsynaptic Currents in Hippocampal CA3 Pyramidal Neurons Are of Mossy Fiber Origin

1997 ◽  
Vol 77 (3) ◽  
pp. 1075-1086 ◽  
Author(s):  
Darrell A. Henze ◽  
J. Patrick Card ◽  
German Barrionuevo ◽  
Yezekiel Ben-Ari
Keyword(s):  
Rise Time ◽  
Large Amplitude ◽  
Mossy Fiber ◽  
Pyramidal Cells ◽  
Peak Amplitude ◽  
Γ Irradiation ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
The Mean ◽  
Ca3 Pyramidal Cells

Henze, Darrell A., J. Patrick Card, German Barrionuevo, and Yezekiel Ben-Ari. Large amplitude miniature excitatory postsynaptic currents in hippocampal CA3 pyramidal neurons are of mossy fiber origin. J. Neurophysiol. 77: 1075–1086, 1997. Neonatal (P0) γ-irradiation was used to lesion selectively the mossy fiber (MF) synaptic input to CA3 pyramidal cells. This lesion caused a >85% reduction in the MF input as determined by quantitative assessment of the number of dynorphin immunoreactive MF boutons. Theγ-irradiation lesion caused a reduction in the mean number of miniature excitatory postsynaptic currents (mEPSCs) recorded from CA3 pyramidal cells (2,292 vs. 1,429/3-min period; n = 10). The lesion also caused a reduction in the mean mEPSC peak amplitude from 19.1 ± 0.45 to 14.6 ± 0.49 pA (mean ± SE; peak conductance 238.8 ± 5.6 to 182.0 ± 6.1 pS). Similarly, there was a reduction in the mean 10–85% rise time from 1.72 ± 0.02 ms to 1.42 ± 0.04 ms. The effects of the γ-irradiation on both mEPSC amplitude and 10–85% rise time were significant at P < 0.002 and P < 0.005 (2-tailed Kolmogorov-Smirnov test). Based on the selectivity of the γ-irradiation, MF and non-MF mEPSC amplitude and 10–85% rise-time distributions were calculated. Both the amplitude and 10–85% rise-time distributions showed extensive overlap between the MF and non-MF mediated mEPSCs. The MF mEPSC distributions had a mean peak amplitude of 24.6 pA (307.5 pS) and a mean 10–85% rise time of 2.16 ms. The non-MF mEPSC distributions had a mean peak amplitude of 12.2 pA (152.5 pS) and 10–85% rise time of 1.26 ms. The modes of the amplitude distributions were the same at 5 pA (62 pS). The MF and non-MF mEPSC amplitude and 10–85% rise-time distributions were significantly different at P ≪ 0.001 (1-tailed, large sample Kolmogorov-Smirnov test). The data demonstrate that the removal of the MF synaptic input to CA3 pyramidal cells leads to the absence of the large amplitude mEPSCs that are present in control recordings.

Effects of Halothane on Glutamate Receptor-mediated Excitatory Postsynaptic Currents

1995 ◽  
Vol 83 (1) ◽  
pp. 109-119. ◽  
Author(s):  
Misha Perouansky ◽  
Dimitri Baranov ◽  
Michael Salman ◽  
Yoel Yaari
Keyword(s):  
Glutamate Receptor ◽  
Glutamate Release ◽  
Pyramidal Cells ◽  
Receptor Subtype ◽  
Excitatory Postsynaptic Currents ◽  
Ca1 Pyramidal Cells ◽  
Postsynaptic Currents ◽  
High Concentrations

Background The effects of halothane on excitatory synaptic transmission in the central nervous system of mammals have been studied in vivo and in vitro in several investigations with partially contradicting results. Direct measurements of the effects of halothane on isolated glutamate receptor-mediated (glutamatergic) excitatory postsynaptic currents (EPSCs), however, have not been reported to date. Methods The effects of halothane on glutamatergic EPSCs were studied in vitro by using tight-seal, whole-cell recordings from CA1 pyramidal cells in thin slices from the adult mouse hippocampus. The EPSCs were pharmacologically isolated into their non-N-methyl-D-aspartate (non-NMDA) and NMDA receptor-mediated components by using selective antagonists. The effects of halothane on EPSC amplitude and kinetics were analyzed at various membrane potentials and were compared with its effects on currents evoked by exogenously applied glutamatergic agonists. Results Halothane (0.2-5.1%; 0.37-2.78 mM) reversibly blocked non-NMDA and NMDA EPSCs. This effect was voltage independent; concentrations producing 50% inhibition were 0.87% (0.66 mM) and 0.69% (0.57 mM), respectively. Currents induced by bath-applied glutamatergic agonists were not affected even by the high concentrations of halothane. Conclusions Halothane depresses glutamatergic EPSCs irrespective of receptor subtype, most likely by inhibition of glutamate release.

Development of Excitatory Circuitry in the Hippocampus

1998 ◽  
Vol 79 (4) ◽  
pp. 2013-2024 ◽  
Author(s):  
Albert Y. Hsia ◽  
Robert C. Malenka ◽  
Roger A. Nicoll
Keyword(s):  
Synaptic Transmission ◽  
Action Potentials ◽  
Pyramidal Cells ◽  
Excitatory Synaptic Transmission ◽  
Developmental Strategy ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Quantal Size ◽  
Physiological Approach ◽  
Local Circuitry

Hsia, Albert Y., Robert C. Malenka, and Roger A. Nicoll. Development of excitatory circuitry in the hippocampus. J. Neurophysiol. 79: 2013–2024, 1998. Assessing the development of local circuitry in the hippocampus has relied primarily on anatomic studies. Here we take a physiological approach, to directly evaluate the means by which the mature state of connectivity between CA3 and CA1 hippocampal pyramidal cells is established. Using a technique of comparing miniature excitatory postsynaptic currents (mEPSCs) to EPSCs in response to spontaneously occurring action potentials in CA3 cells, we found that from neonatal to adult ages, functional synapses are created and serve to increase the degree of connectivity between CA3-CA1 cell pairs. Neither the probability of release nor mean quantal size was found to change significantly with age. However, the variability of quantal events decreases substantially as synapses mature. Thus in the hippocampus the developmental strategy for enhancing excitatory synaptic transmission does not appear to involve an increase in the efficacy at individual synapses, but rather an increase in the connectivity between cell pairs.

Presynaptic Modulation of Synaptic Transmission by Pregnenolone Sulfate as Studied by Optical Recordings

2005 ◽  
Vol 94 (6) ◽  
pp. 4131-4144 ◽  
Author(s):  
Ling Chen ◽  
Masahiro Sokabe
Keyword(s):  
Synaptic Transmission ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Receptor Activation ◽  
Optical Recording ◽  
Perforant Path ◽  
Dependent Manner ◽  
Pregnenolone Sulfate ◽  
Voltage Sensitive Dyes ◽  
Dose Dependent

The effects of pregnenolone sulfate (PREGS), a putative neurosteroid, on the transmission of perforant path–granule cell synapses were investigated with an optical recording technique in rat hippocampal slices stained with voltage-sensitive dyes. Application of PREGS to the bath solution resulted in an acute augmentation of EPSP in a dose-dependent manner. The PREGS effect was dependent on the extracellular Ca2+ concentration ([Ca2+]o), but independent of NMDA receptor activation. PREGS caused a decrease in paired-pulse facilitation, which implies that PREGS positively modulates presynaptic neurotransmitter releases. Firmer support for this mechanism was that PREGS augmented the synaptically induced glial depolarization (SIGD) that reflects the activity of electrogenic glutamate transporters in glial cells during the uptake of released glutamate. The selective α7nAChR antagonist α-BGT or MLA prevented the SIGD increase by PREGS. Furthermore DMXB, a selective α7nAChR agonist, mimicked the PREGS effect on SIGD and antagonized the effect of PREGS. The presynaptic effect of PREGS was partially attenuated by the L-type Ca2+ channel (VGCC) blocker nifedipine. Based on these findings, we proposed a novel mechanism underlying the facilitated synaptic transmission by PREGS: this neurosteroid sensitizes presynaptic α7nAChR that is followed by an activation of L-type VGCC to increase the presynaptic glutamate release.

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.

Evidence from simultaneous intracellular recordings in rat hippocampal slices that area CA3 pyramidal cells innervate dentate hilar mossy cells

1994 ◽  
Vol 72 (5) ◽  
pp. 2167-2180 ◽  
Author(s):  
H. E. Scharfman
Keyword(s):  
Pyramidal Cell ◽  
Action Potentials ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Probability Of Failure ◽  
Mossy Cells ◽  
Mossy Cell ◽  
Ca3 Pyramidal Cells ◽  
Area Ca3

1. Simultaneous intracellular recordings of area CA3 pyramidal cells and dentate hilar “mossy” cells were made in rat hippocampal slices to test the hypothesis that area CA3 pyramidal cells excite mossy cells monosynaptically. Mossy cells and pyramidal cells were differentiated by location and electrophysiological characteristics. When cells were impaled near the border of area CA3 and the hilus, their identity was confirmed morphologically after injection of the marker Neurobiotin. 2. Evidence for monosynaptic excitation of a mossy cell by a pyramidal cell was obtained in 7 of 481 (1.4%) paired recordings. In these cases, a pyramidal cell action potential was followed immediately by a 0.40 to 6.75 (mean, 2.26) mV depolarization in the simultaneously recorded mossy cell (mossy cell membrane potentials, -60 to -70 mV). Given that pyramidal cells used an excitatory amino acid as a neurotransmitter (Cotman and Nadler 1987; Ottersen and Storm-Mathisen 1987) and recordings were made in the presence of the GABAA receptor antagonist bicuculline (25 microM), it is likely that the depolarizations were unitary excitatory postsynaptic potentials (EPSPs). 3. Unitary EPSPs of mossy cells were prone to apparent “failure.” The probability of failure was extremely high (up to 0.72; mean = 0.48) if the effects of all presynaptic action potentials were examined, including action potentials triggered inadvertently during other spontaneous EPSPs of the mossy cell. Probability of failure was relatively low (as low as 0; mean = 0.24) if action potentials that occurred during spontaneous activity of the mossy cell were excluded. These data suggest that unitary EPSPs produced by pyramidal cells are strongly affected by concurrent synaptic inputs to the mossy cell. 4. Unitary EPSPs were not clearly affected by manipulation of the mossy cell's membrane potential. This is consistent with the recent report that area CA3 pyramidal cells innervate distal dendrites of mossy cells (Kunkel et al. 1993). Such a distal location also may contribute to the high incidence of apparent failures. 5. Characteristics of unitary EPSPs generated by pyramidal cells were compared with the properties of the unitary EPSPs produced by granule cells. In two slices, pyramidal cell and granule cell inputs to the same mossy cell were compared. In other slices, inputs to different mossy cells were compared. In all experiments, unitary EPSPs produced by granule cells were larger in amplitude but similar in time course to unitary EPSPs produced by pyramidal cells. Probability of failure was lower and paired-pulse facilitation more common among EPSPs triggered by granule cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Membrane Potential of CA3 Hippocampal Pyramidal Cells During Postnatal Development

2003 ◽  
Vol 90 (5) ◽  
pp. 2964-2972 ◽  
Author(s):  
Roman Tyzio ◽  
Anton Ivanov ◽  
Cristophe Bernard ◽  
Gregory L. Holmes ◽  
Yehezkiel Ben-Ari ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Postnatal Development ◽  
Developmental Change ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Whole Cell ◽  
Perforated Patch ◽  
Ca3 Pyramidal Cells ◽  
Whole Cell Recordings

A depolarized resting membrane potential has long been considered to be a universal feature of immature neurons. Despite the physiological importance, the underlying mechanisms of this developmental phenomenon are poorly understood. Using perforated-patch, whole cell, and cell-attached recordings, we measured the membrane potential in CA3 pyramidal cells in hippocampal slices from postnatal rats. With gramicidin perforated-patch recordings, membrane potential was –44 ± 4 (SE) mV at postnatal days P0–P2, and it progressively shifted to –67 ± 2 mV at P13–15. A similar developmental change of the membrane potential has been also observed with conventional whole cell recordings. However, the value of the membrane potential deduced from the reversal potential of N-methyl-d-aspartate channels in cell-attached recordings did not change with age and was –77 ± 2 mV at P2 and –77 ± 2 mV at P13–14. The membrane potential measured using whole cell recordings correlated with seal and input resistance, being most depolarized in neurons with high, several gigaohms, input resistance and low seal resistance. Simulations revealed that depolarized values of the membrane potential in whole cell and perforated-patch recordings could be explained by a shunt through the seal contact between the pipette and membrane. Thus the membrane potential of CA3 pyramidal cells appears to be strongly negative at birth and does not change during postnatal development.

The dendritic origins of penicillin-induced epileptogenesis in CA3 hippocampal pyramidal cells

1986 ◽  
Vol 56 (6) ◽  
pp. 1718-1738 ◽  
Author(s):  
J. W. Swann ◽  
R. J. Brady ◽  
R. J. Friedman ◽  
E. J. Smith
Keyword(s):  
Cell Body ◽  
Average Distance ◽  
Hippocampal Slices ◽  
Current Source ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Large Current ◽  
Hippocampal Ca3 ◽  
Ca3 Pyramidal Cells ◽  
Negative Field

Experiments were performed in order to identify the sites of epileptiform burst generation in rat hippocampal CA3 pyramidal cells. A subsequent slow field potential was studied, which is associated with afterdischarge generation. Laminar field potential and current source-density (CSD) methods were employed in hippocampal slices exposed to penicillin. Simultaneous intracellular and extracellular field recordings from the CA3 pyramidal cell body layer showed that whenever an epileptiform burst was recorded extracellularly, individual CA3 neurons underwent an intense depolarization shift. In extracellular records a slow negative field potential invariably followed epileptiform burst generation. In approximately 10% of slices, synchronous afterdischarges rode on the envelope of this negative field potential. Intracellularly a depolarizing afterpotential followed the depolarization shift and was coincident with the extracellular slow negative field potential. A one-dimensional CSD analysis performed perpendicular to the CA3 cell body layer showed that during epileptiform burst generation large current sinks occur simultaneously in the central portions of both the apical and basilar dendrites. The average distance of the peak amplitude for these sinks from the center of the cell body layer was 175 +/- 46.8 microns and 158 +/- 25.0 microns, respectively. A large current source was recorded in the cell body layer. Smaller current sources were observed in the distal portions of the dendritic layers. During the postburst slow field potential a current sink was recorded at the edge of the cell body layer in stratum oriens--a region referred to as the infrapyramidal zone. Simultaneous with the current sink recorded there, smaller sinks were often observed in the dendritic layers that appeared to be "tails" or prolongations of the currents underlying burst generation. Two-dimensional analyses of these field potentials were performed on planes parallel and perpendicular to the exposed surface of the slice. Isopotential contours showed that the direction of extracellular current is mainly orthogonal to the CA3 laminae. Correction of CSD estimates made perpendicular to the cell body layer for current flowing in the other direction did not alter the location of computed current sources and sinks. In order to show that the dendritic currents associated with epileptiform burst generation were active sinks, tetrodotoxin (TTX) was applied locally to the dendrites where the current sinks were recorded.(ABSTRACT TRUNCATED AT 400 WORDS)

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