Dendritic Na+ channels amplify EPSPs in hippocampal CA1 pyramidal cells

1996 ◽  
Vol 76 (4) ◽  
pp. 2181-2191 ◽  
Author(s):  
R. Lipowsky ◽  
T. Gillessen ◽  
C. Alzheimer
Keyword(s):  
Receptor Antagonist ◽  
Gabab Receptor ◽  
Local Density ◽  
Pyramidal Cells ◽  
Apical Dendrite ◽  
Stratum Radiatum ◽  
Gamma Aminobutyric Acid ◽  
Na Channels ◽  
Voltage Range ◽  
Gabaa Receptor Antagonist

1. Whole cell recordings were performed on the somata of CA1 pyramidal neurons in the rat hippocampal slice preparation Remote synaptic events were evoked by electrical stimulation of Schaffer collateral/commissural fibers in outer stratum radiatum. To isolate non-N-methyl-D-aspartate (NMDA)-mediated excitatory postsynaptic potentials (EPSPs), bath solutions contained the NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acid (D-APV; 30 microM), the gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline (10 microM), and the GABAB receptor antagonists, CGP 35348 (30 microM) or, in some experiments, saclofen (100 microM). 2. Local application of tetrodotoxin (TTX; 0.5-10 microM) into the proximal region of the apical dendrite reduced the peak amplitude of somatically recorded EPSPs by 28% on average. In contrast to dendritic TTX application, injection of TTX into the axosomatic region of the recorded neuron reduced EPSP amplitude by only 12% on average. 3. Spill-over of dendritically applied TTX into stratum pyramidale or into outer stratum radiatum was ruled out experimentally: somatic action potentials and field EPSPs recorded near the stimulation site in outer stratum radiatum remained unaffected by local TTX application. 4. Variations of somatic membrane potential revealed a strong voltage dependence of EPSP reduction after dendritic TTX application with the effect increasing substantially with membrane depolarization. Together with the field recordings from stratum radiatum, this finding argues strongly against a predominantly presynaptic site of TTX action. 5. We therefore ascribe the EPSP decrease after local TTX application to the proximal dendrite to suppression of dendritic Na+ channels, which we assume to give rise to a noninactivating (persistent) Na+ current (INaP) in the subthreshold voltage range. Our data suggest that presumed dendritic INaP produces considerable elevation of remote excitatory signals, thereby compensating for much of their electrotonic attenuation. 6. The experimental findings were related to computer simulations performed on a reduced compartmental model of the CA1 neuron. Because the experimental evidence available so far yields only indirect clues on the strength and distribution of INaP, we allowed considerable variations in these parameters. We also varied both size and location of synaptic input. 7. The major conclusions drawn from these simulations are the following: somatic INaP alone produces little EPSP enhancement; INaP density at the axon hillock/initial segment has to be at least twice the density at the soma to produce substantial EPSP amplification; depending on the density and distribution of dendritic INaP, < or = 80% of a remote synaptic potential arrives at the soma (compared with only 52% in a passive dendrite); synaptic potentials receive progressively more elevation by dendritic INaP the stronger they are; even if restricted to the proximal segment of the apical dendrite, INaP also affects dendritic processing at more distal segments; and spatial distribution rather than local density appears to be the most important parameter determining the role of dendritic INaP in synaptic integration.

GABA stimulation of gonadotropin-II release in goldfish: involvement of GABAA receptors, dopamine, and sex steroids

1993 ◽  
Vol 265 (2) ◽  
pp. R348-R355 ◽  
Author(s):  
V. L. Trudeau ◽  
B. D. Sloley ◽  
R. E. Peter
Keyword(s):  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Receptor Agonist ◽  
Gabab Receptor ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Turnover Rates ◽  
Pharmacological Agents ◽  
Gabaa Receptor Antagonist ◽  
Gonadotropin Ii

The involvement of gamma-aminobutyric acid (GABA) in regulation of pituitary gonadotropin-II (GTH-II) release was studied in the goldfish. Intraperitoneal injection of GABA (300 micrograms/g) stimulated an increase in serum GTH-II levels at 30 min postinjection. The GABAA receptor agonist muscimol (0.1-10 micrograms/g) stimulated GTH-II in a dose-dependent manner. Baclofen, a GABAB receptor agonist, had a small but significant stimulatory effect at 1 and 10 micrograms/g; the amount of GTH-II released in response to baclofen was significantly less (P < 0.05) than that released by muscimol. Pretreatment of goldfish with bicuculline, a GABAA receptor antagonist, but not saclofen, a GABAB receptor antagonist, blocked the stimulatory effect of GABA on serum GTH-II. Elevation of brain and pituitary GABA levels with the GABA transaminase inhibitor, gamma-vinyl-GABA (GVG), decreased hypothalamic and pituitary dopamine (DA) turnover rates, indicating that GABA may stimulate GTH-II release in the goldfish by decreasing dopaminergic inhibition of GTH-II release. The release of GTH-II stimulated by muscimol and GVG was potentiated by pharmacological agents that decrease inhibitory dopaminergic tone, indicating that DA may also inhibit GABA-stimulated GTH-II release. Based on the linear 24-h accumulation of GABA in brain and pituitary after GVG injection, implantation of testosterone, estradiol, or progesterone, previously shown to regulate the serum GTH-II release response to gonadotropin-releasing hormone and GABA, was also found to modulate GABA synthesis in the brain and pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Dynorphin and GABAA Receptor Signaling Contribute to Progesterone’s Inhibition of the LH Surge in Female Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (5) ◽  
Author(s):  
Yali Liu ◽  
Xiaofeng Li ◽  
Xi Shen ◽  
Deyana Ivanova ◽  
Geffen Lass ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Gabab Receptor ◽  
Gaba Release ◽  
Estradiol Benzoate ◽  
Receptor Signaling ◽  
Gamma Aminobutyric Acid ◽  
Lh Surge ◽  
Female Mice ◽  
Gabaa Receptor Antagonist

Abstract Progesterone can block estrogen-induced luteinising hormone (LH) surge secretion and can be used clinically to prevent premature LH surges. The blocking effect of progesterone on the LH surge is mediated through its receptor in the anteroventral periventricular nucleus (AVPV) of the hypothalamus. However, the underlying mechanisms are unclear. The preovulatory LH surge induced by estrogen is preceded by a significant reduction in hypothalamic dynorphin and gamma-aminobutyric acid (GABA) release. To test the detailed roles of dynorphin and GABA in an LH surge blockade by progesterone, ovariectomized and 17β-estradiol capsule-implanted (OVX/E2) mice received simultaneous injections of estradiol benzoate (EB) and progesterone (P) or vehicle for 2 consecutive days. The LH level was monitored from 2:30 pm to 8:30 pm at 30-minute intervals. Progesterone coadministration resulted in the LH surge blockade. A continuous microinfusion of the dynorphin receptor antagonist nor-BNI or GABAA receptor antagonist bicuculline into the AVPV from 3:00 pm to 7:00 pm reversed the progesterone-mediated blockade of the LH surge in 7 of 9 and 6 of 10 mice, respectively. In addition, these LH surges started much earlier than the surge induced by estrogen alone. However, 5 of 7 progesterone-treated mice did not show LH surge secretion after microinfusion with the GABAB receptor antagonist CGP-35348. Additionally, peripheral administration of kisspeptin-54 promotes LH surge-like release in progesterone treated mice. These results demonstrated that the progesterone-mediated suppression of the LH surge is mediated by an increase in dynorphin and GABAA receptor signaling acting though kisspeptin neurons in the AVPV of the hypothalamus in female mice.

Enteric GABA: mode of action and role in the regulation of the peristaltic reflex

1992 ◽  
Vol 262 (4) ◽  
pp. G690-G694 ◽  
Author(s):  
J. R. Grider ◽  
G. M. Makhlouf
Keyword(s):  
Receptor Antagonist ◽  
Motor Neurons ◽  
Gabaa Receptors ◽  
Mode Of Action ◽  
Gabab Receptor ◽  
Circular Muscle ◽  
Gamma Aminobutyric Acid ◽  
Peristaltic Reflex ◽  
Gaba Neurons ◽  
Gabaa Receptor Antagonist

The mode of action of gamma-aminobutyric acid (GABA) and the role of myenteric GABA neurons in the regulation of peristalsis were examined in various preparations of rat colonic muscle. GABA had no contractile, relaxant, or modulatory effect on smooth muscle cells isolated from the circular muscle layer. In innervated circular muscle strips, GABA elicited concentration-dependent relaxation accompanied by release of vasoactive intestinal peptide (VIP). Relaxation and VIP release were inhibited by tetrodotoxin and by the GABAA receptor antagonist bicuculline but not by the GABAB receptor antagonist phaclofen. Relaxation was inhibited by the VIP receptor antagonist VIP-(10-28) implying that VIP release was coupled to muscle relaxation. Relaxation was augmented by atropine implying that GABA also activated cholinergic neurons causing release of acetylcholine that attenuated the relaxant response. This pharmacological profile was evident when GABA was released from intrinsic GABA neurons during peristalsis induced by radial stretch. Blockade of GABAA receptors with bicuculline inhibited the descending relaxation mediated by VIP motor neurons and the ascending contraction mediated by cholinergic motor neurons. Stimulation of these receptors with exogenous GABA had the opposite effect. We conclude that on release from myenteric neurons, GABA acts via GABAA receptors on cholinergic and VIP motor neurons responsible for the two components of the peristaltic reflex.

Hippocampal CA1 lacunosum-moleculare interneurons: modulation of monosynaptic GABAergic IPSCs by presynaptic GABAB receptors

1995 ◽  
Vol 74 (5) ◽  
pp. 2126-2137 ◽  
Author(s):  
R. Khazipov ◽  
P. Congar ◽  
Y. Ben-Ari
Keyword(s):  
Receptor Antagonist ◽  
Transmitter Release ◽  
Gabab Receptor ◽  
Molecular Layer ◽  
Pyramidal Cells ◽  
Gabab Receptors ◽  
Stratum Radiatum ◽  
Paired Pulse ◽  
High Level ◽  
Paired Pulse Depression

1. Whole cell patch-clamp recordings were employed to characterize monosynaptic inhibitory postsynaptic currents (IPSCs) in morphologically and electrophysiologically identified interneurons located in the stratum lacunosum moleculare, or near the border of the stratum radiatum (LM interneurons), in the CA1 region of hippocampal slices taken from 3- to 4-wk-old rats. Monosynaptic IPSCs, evoked in the presence of glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM) and D-2-amino-5-phosphopentanoate (APV; 50 microM) were biphasic. The gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline (20 microM), blocked the fast IPSC, and the slow IPSC was blocked by the GABAB receptor antagonist CGP35348 (500 microM). 2. Monosynaptic IPSCs were evoked by electrical stimulation in several distant regions including the stratum radiatum, the stratum oriens, the stratum lacunosum-moleculare, and the molecular layer of dentate gyrus, suggesting an extensive network of inhibitory interneurons in the hippocampus. In paired recordings of CA1 interneurons and pyramidal cells, IPSCs were evoked by electrical stimulation of most of these distal regions with the exception of the molecular layer of dentate gyrus, which evoked an IPSC only in LM interneurons. 3. Frequent (> 0.1 Hz) stimulation depressed the evoked IPSCs. With a paired-pulse protocol, the second IPSC was depressed and the maximal depression (40-50%) was observed with an interstimulus interval of 100-200 ms. 4. The GABAB receptor agonist baclofen (1 microM) reduced the amplitude of evoked IPSCs and the paired-pulse depression of the second IPSC. The GABAB receptor antagonist CGP35348 (0.5-1 mM) had no significant effect on the amplitude of isolated IPSCs. However, CGP35348 reduced but did not fully block paired-pulse depression, suggesting that this depression is partly due to the activation of presynaptic GABAB receptors. 5. The paired-pulse depression depended on the level of transmitter release. Potentiation of synaptic release of GABA, by increasing the extracellular Ca2+ concentration to 4 mM and reducing the extracellular Mg2+ concentration to 0.1 mM, enhanced the depression. Reduction of transmitter release by increasing extracellular Mg2+ concentration to 7 mM diminished the paired-pulse depression of IPSCs. After potentiation of transmitter release, CGP35348 was less efficient in reducing the paired-pulse depression, suggesting that enhancement of depression by high-calcium/low-magnesium medium was preferentially due to the potentiation of a GABAB-independent component. 6. In summary, monosynaptic IPSCs recorded in LM interneurons show similar features to those recorded in pyramidal cells. The strong correlation between the level of transmitter release and the degree of paired-pulse depression may have important physiological consequences, because in synapses with a high level of activity and a high level of GABA release, inhibition is powerful, but depression can develop more readily.

Oscillatory synaptic interactions between ventroposterior and reticular neurons in mouse thalamus in vitro

1994 ◽  
Vol 72 (4) ◽  
pp. 1993-2003 ◽  
Author(s):  
R. A. Warren ◽  
A. Agmon ◽  
E. G. Jones
Keyword(s):  
Receptor Antagonist ◽  
Gabab Receptor ◽  
Initial Response ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Excitatory Postsynaptic Potential ◽  
Postsynaptic Potential ◽  
Synaptic Interactions ◽  
Gabaa Receptor Antagonist

1. The thalamic reticular nucleus (RTN) has reciprocal connections with relay neurons in the dorsal thalamus. We used whole cell recording in a mouse in vitro slice preparation maintained at room temperature to study the synaptic interactions between the RTN and the ventroposterior thalamic nucleus (VP) during evoked low-frequency oscillations. 2. After a single electrical stimulus of the internal capsule, postsynaptic potentials (PSPs) were recorded in all VP and RTN neurons. In 76% of slices, there was an initial response followed by recurrent PSPs lasting for up to 8 s and with a frequency of approximately 2 Hz in both the VP and RTN. 3. In RTN neurons the initial response consisted of a fast excitatory postsynaptic potential (EPSP) that generated a burst of action potentials. Recurrent PSPs consisted of barrages of EPSPs that often reached burst threshold. The structure of subthreshold EPSP barrages in RTN neurons suggested that they were generated by bursting VP neurons. 4. In VP neurons the stimulus usually evoked a small EPSP followed by a large inhibitory postsynaptic potential (IPSP) that was often followed by a rebound burst. This initial response was often followed by a series of recurrent IPSPs presumably generated by RTN bursts, because intrinsic inhibitory neurons are absent in rodent VP. 5. IPSPs in VP neurons and recurrent EPSPs in RTN neurons were completely abolished by application of a gamma-aminobutyric acid-A (GABAA) receptor antagonist. A GABAB receptor antagonist produced no or little change in either the initial or recurrent response. 6. Recurrent IPSPs in VP neurons were abolished by glutamate receptor antagonists before the initial IPSP, which always remained stimulus dependent. 7. The dependency of recurring IPSPs in VP and recurring EPSPs in RTN upon GABA-mediated inhibition and excitatory amino acid-mediated excitation, plus the character of recurring EPSPs in the RTN strongly suggest that the recurring events were generated through reverse-reciprocal synaptic interactions between VP and RTN neurons. These synaptic interactions most likely play an important role in thalamic oscillations in behavior.

scholarly journals Acetylcholine release inhibits distinct excitatory inputs onto hippocampal CA1 pyramidal neurons via different cellular and network mechanisms

2019 ◽  
Author(s):  
Priyodarshan Goswamee ◽  
A. Rory McQuiston
Keyword(s):  
Receptor Antagonist ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Inhibitory Interneuron ◽  
Stratum Radiatum ◽  
Synaptic Efficacy ◽  
Ach Release ◽  
Paired Pulse ◽  
Ca1 Pyramidal Cells ◽  
Hippocampal Ca1

AbstractIn hippocampal CA1, muscarinic acetylcholine (ACh) receptor (mAChR) activation via exogenous application of cholinergic agonists has been shown to presynaptically inhibit Schaffer collateral (SC) glutamatergic inputs in stratum radiatum (SR), and temporoammonic (TA) and thalamic nucleus reuniens (RE) glutamatergic inputs in stratum lacunosum-moleculare (SLM). However, steady-state uniform mAChR activation may not mimic the effect of ACh release in an intact hippocampal network. To more accurately examine the effect of ACh release on glutamatergic synaptic efficacy, we measured electrically evoked synaptic responses in CA1 pyramidal cells (PCs) following the optogenetic release of ACh in genetically modified mouse brain slices. The ratio of synaptic amplitudes in response to paired-pulse SR stimulation (stimulus 2/stimulus 1) was significantly reduced by the optogenetic release of ACh, consistent with a postsynaptic decrease in synaptic efficacy. The effect of ACh release was blocked by the M3 receptor antagonist 4-DAMP, the GABAB receptor antagonist CGP 52432, inclusion of GDP-β-S, cesium, QX314 in the intracellular patch clamp solution, or extracellular barium. These observations suggest that ACh release decreased SC synaptic transmission through an M3 muscarinic receptor-mediated increase in inhibitory interneuron excitability, which activate GABAB receptors and inwardly rectifying potassium channels on CA1 pyramidal cells. In contrast, the ratio of synaptic amplitudes in response to paired-pulse stimulation in the SLM was increased by ACh release, consistent with presynaptic inhibition. ACh-mediated effects in SLM were blocked by the M2 receptor antagonist AF-DX 116, presumably located on presynaptic terminals. Therefore, our data indicate that ACh release differentially modulates excitatory inputs in SR and SLM of CA1 through different cellular and network mechanisms.

Role of HCO3- ions in depolarizing GABAA receptor-mediated responses in pyramidal cells of rat hippocampus

1993 ◽  
Vol 69 (5) ◽  
pp. 1541-1555 ◽  
Author(s):  
L. M. Grover ◽  
N. A. Lambert ◽  
P. A. Schwartzkroin ◽  
T. J. Teyler
Keyword(s):  
Gabaa Receptor ◽  
Gabab Receptor ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Gamma Aminobutyric Acid ◽  
Free Medium ◽  
Postsynaptic Potentials ◽  
Ca1 Pyramidal Cells ◽  
Ionic Basis

1. Activation of GABAA receptors can produce both hyperpolarizing and depolarizing responses in CA1 pyramidal cells. The hyperpolarizing response is mediated by a Cl- conductance, but the ionic basis of the depolarizing response is not clear. We compared the GABAA receptor-mediated depolarizations induced by synaptically released gamma-aminobutyric acid [GABA; depolarizing inhibitory postsynaptic potentials (dIPSPs)] with those produced by exogenous GABA (depolarizing GABA responses). Short trains of high-frequency (200 Hz) stimuli were used to generate dIPSPs. We found that dIPSPs generated by trains of stimuli and depolarizing responses to exogenous GABA were accompanied by a conductance increase and had a similar reversal potential, indicating a similar ionic basis for both responses. 2. We wished to determine whether an HCO3- current contributed to the GABAA-mediated depolarizations. We found that dIPSPs and depolarizing GABA responses were sensitive to perfusion with HCO3(-)-free medium. Interpretation of these data was complicated by the mixed nature of the responses: dIPSPs were invariably accompanied by conventional, Cl(-)-mediated fast hyperpolarizing IPSPs (fIPSPs), and response to exogenous GABA usually consisted of biphasic hyperpolarizing and depolarizing responses. However, it was sometimes possible to elicit responses to GABA that appeared purely depolarizing (monophasic depolarizing GABA responses). 3. We analyzed monophasic depolarizing GABA responses and found no change in reversal potential when slices were perfused with HCO(3-)-free medium. We also made whole-cell recordings from CA1 pyramidal cells, attempting to reduce [HCO3-]i, and compared the reversal potential for monophasic depolarizing GABA responses with similar responses recorded with fine intracellular microelectrodes. We found no difference in reversal potential. We also examined effects of the carbonic anhydrase inhibitor acetazolamide (ACTZ) on depolarizing GABA responses. ACTZ reduced these responses but did not change their reversal potential. 4. Effects of HCO(3-)-free medium were not specific to GABAA receptor-mediated responses. GABAB receptor-mediated slow IPSPs (sIPSPs) were also reduced, as were excitatory postsynaptic potentials (EPSPs). Analyses of field potentials and spontaneous fIPSPs suggested a decrease in presynaptic excitability during perfusion with HCO(3-)-free medium. In addition, pyramidal cells showed decreased input resistance when perfused with HCO(3-)-free medium. 5. The sensitivity of GABAA receptor-mediated depolarizations to HCO(3-)-free medium can be explained by a decrease in presynaptic excitability and an increased resting conductance in postsynaptic neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Long delay lines for ranging are created by inhibition in the inferior colliculus of the mustached bat

1995 ◽  
Vol 74 (1) ◽  
pp. 1-11 ◽  
Author(s):  
I. Saitoh ◽  
N. Suga
Keyword(s):  
Auditory Cortex ◽  
Receptor Antagonist ◽  
Inferior Colliculus ◽  
Coincidence Detection ◽  
Central Nucleus ◽  
Gamma Aminobutyric Acid ◽  
Delay Lines ◽  
Mustached Bat ◽  
Gabaa Receptor Antagonist ◽  
Medial Geniculate

1. The central auditory system of the mustached bat has arrays of delay-tuned (FM-FM combination-sensitive) neurons in the inferior colliculus, the medial geniculate body, and the auditory cortex. These neurons are tuned to particular echo delays, i.e., target distances. The neural mechanisms for creating the delay-tuned neurons involve delay lines, coincidence detection, and amplification. We have hypothesized that delay lines longer than 4 ms are created by inhibition occurring in the anterolateral division (ALD) of the central nucleus of the inferior colliculus. If this hypothesis is correct, suppression of inhibition occurring in the ALD must shorten the best delays of the collicular, thalamic, and cortical delay-tuned neurons. The aim of the present study is to test this hypothesis. Responses of single delay-tuned neurons in the FM-FM area of the auditory cortex were recorded with a tungsten-wire microelectrode, and the effects of iontophoretic microinjections of strychnine (STR) and/or bicuculline methiodide (BMI) into the ALD were examined on the responses of these neurons. 2. STR (glycine receptor antagonist) and/or BMI [gamma-aminobutyric acid-A (GABAA) receptor antagonist] injections into the ALD shortened the best delays of delay-tuned neurons in the FM-FM area with little change in their response patterns. The longer the best delay of a delay-tuned neuron, the larger the amount of shortening. 3. Inhibition mediated by glycine receptors plays a larger role in creating delay lines than that mediated by GABAA receptors, because STR and BMI, respectively, shortened the best delay of 91 and 74% of the neurons with best delays longer than 4.5 ms. 4. BMI has no effect on the best delays of delay-tuned neurons that were tuned to echo delays shorter than 4.5 ms. 5. The present data support the hypothesis that long delay lines utilized by delay-tuned neurons are created by inhibition occurring in the ALD of the inferior colliculus. However, the amount of shortening in delay lines by STR and/or BMI was generally smaller than that predicted by a neural network model. Therefore the present study partially answers the questions of where and how long delay lines were created.

Agent-selective Effects of Volatile Anesthetics on GABAAReceptor–mediated Synaptic Inhibition in Hippocampal Interneurons

2001 ◽  
Vol 94 (2) ◽  
pp. 340-347 ◽  
Author(s):  
Koichi Nishikawa ◽  
M. Bruce MacIver
Keyword(s):  
Gabaa Receptor ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Volatile Anesthetics ◽  
Stratum Radiatum ◽  
Synaptic Inhibition ◽  
Gamma Aminobutyric Acid ◽  
Ca1 Region ◽  
Whole Cell Patch Clamp ◽  
Cortical Regions

Background A relatively small number of inhibitory interneurons can control the excitability and synchronization of large numbers of pyramidal cells in hippocampus and other cortical regions. Thus, anesthetic modulation of interneurons could play an important role for the maintenance of anesthesia. The aim of this study was to compare effects produced by volatile anesthetics on inhibitory postsynaptic currents (IPSCs) of rat hippocampal interneurons. Methods Pharmacologically isolated gamma-aminobutyric acid type A (GABAA) receptor-mediated IPSCs were recorded with whole cell patch-clamp techniques in visually identified interneurons of rat hippocampal slices. Neurons located in the stratum radiatum-lacunosum moleculare of the CA1 region were studied. The effects of clinically relevant concentrations (1.0 rat minimum alveolar concentration) of halothane, enflurane, isoflurane, and sevoflurane were compared on kinetics of both stimulus-evoked and spontaneous GABAA receptor-mediated IPSCs in interneurons. Results Halothane (1.2 vol% approximately 0.35 mm), enflurane (2.2 vol% approximately 0.60 mm), isoflurane (1.4 vol% approximately 0.50 mm), and sevoflurane (2.7 vol% approximately 0.40 mm) preferentially depressed evoked IPSC amplitudes to 79.8 +/- 9.3% of control (n = 5), 38.2 +/- 8.6% (n = 6), 52.4 +/- 8.4% (n = 5), and 46.1 +/- 16.0% (n = 8), respectively. In addition, all anesthetics differentially prolonged the decay time constant of evoked IPSCs to 290.1 +/- 33.2% of control, 423.6 +/- 47.1, 277.0 +/- 32.2, and 529 +/- 48.5%, respectively. The frequencies of spontaneous IPSCs were increased by all anesthetics (twofold to threefold). Thus, the total negative charge transfer mediated by GABAA receptors between synaptically connected interneurons was enhanced by all anesthetics. Conclusions Volatile anesthetics differentially enhanced GABAA receptor-mediated synaptic inhibition in rat hippocampal interneurons, suggesting that hippocampal interneuron circuits are depressed by these anesthetics in an agent-specific manner.

Use-dependent depression of IPSPs in rat hippocampal pyramidal cells in vitro

1985 ◽  
Vol 53 (2) ◽  
pp. 557-571 ◽  
Author(s):  
M. McCarren ◽  
B. E. Alger
Keyword(s):  
Membrane Potential ◽  
Conditioning Stimulus ◽  
Pyramidal Cells ◽  
Repetitive Stimulation ◽  
Stratum Radiatum ◽  
Resting Potential ◽  
Masking Effect ◽  
Extracellular Potassium ◽  
Gamma Aminobutyric Acid ◽  
Hippocampal Pyramidal Cells

We have used intracellular recording techniques to study the use-dependence of evoked inhibitory postsynaptic potentials (IPSPs) in rat CA1 hippocampal pyramidal cells. We determined reversal potentials and conductance changes associated with IPSPs and responses to directly applied gamma-aminobutyric acid (GABA). The IPSP depression could be seen after a single conditioning stimulus. This depression appeared to be due primarily to a 50% decrease in IPSP conductance (gIPSP). Trains of stimulating pulses (50 pulses at 5 or 10 Hz) produced more pronounced effects than a single conditioning pulse. Suprathreshold repetitive stimulation of stratum radiatum (SR) produced epileptiform burst firing and greater depression of IPSPs than did alvear (ALV) or subthreshold SR stimulation. During suprathreshold SR stimulation the IPSP was nearly abolished and the membrane potential could become less negative than the resting potential. A masking effect of facilitated depolarizing potentials on IPSPs was unlikely since IPSPs accompanied by little or no depolarizing potential were also depressed by SR trains. The 75% reduction in IPSP conductance found after repetitive stimulation confirmed that an overlapping conductance was not responsible for the depression of the IPSP. The GABA-induced conductance increase was not depressed by identical trains. Trains of stimulation induced depolarizing shifts in equilibrium potentials for the IPSP (EIPSP) and GABA (EGABA) of approximately 10 mV. These shifts were always greater after SR trains than after ALV trains. Simultaneous recordings of membrane potential and extracellular potassium concentration ([K+]o) with K+-sensitive microelectrodes revealed a direct correlation between the two during a stimulus train. Membrane potential depolarized as much as 18 mV from the peak of the IPSP and [K+]o could increase to a maximum of 10 mM during some trains. A depressant effect (of approximately 50%) of K+ on IPSPs was demonstrated by brief pressure ejection of K+ near the soma. We conclude that repetitive stimulation depresses gIPSP and shifts EIPSP in the depolarizing direction. Whereas gIPSP began to decline after a single conditioning pulse, the additional depression of IPSPs produced by stimulus trains was due in large part to shifts in EIPSP. Depression of gIPSP was not due to desensitization or block of ionic conductances, since gGABA was not reduced. The EIPSP may change as a result of increases in [K+]o.

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