Sevoflurane Induced Suppression of Inhibitory Synaptic Transmission Between Soma-Soma Paired Lymnaea Neurons

1999 ◽  
Vol 82 (5) ◽  
pp. 2812-2819 ◽  
Author(s):  
Toshiro Hamakawa ◽  
Zhong-Ping Feng ◽  
Nikita Grigoriv ◽  
Takuya Inoue ◽  
Mayumi Takasaki ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Cell Voltage ◽  
Synaptic Depression ◽  
Membrane Properties ◽  
Inhibitory Synapses ◽  
General Anesthetics ◽  
Inhibitory Synaptic Transmission ◽  
Transmitter Receptors ◽  
Lymnaea Neurons

The cellular and synaptic mechanisms by which general anesthetics affect cell-cell communications in the nervous system remain poorly defined. In this study, we sought to determine how clinically relevant concentrations of sevoflurane affected inhibitory synaptic transmission between identified Lymnaea neurons in vitro. Inhibitory synapses were reconstructed in cell culture, between the somata of two functionally well-characterized neurons, right pedal dorsal 1 (RPeD1, the giant dopaminergic neuron) and visceral dorsal 4 (VD4). Clinically relevant concentrations of sevoflurane (1–4%) were tested for their effects on synaptic transmission and the intrinsic membrane properties of soma-soma paired cells. RPeD1- induced inhibitory postsynaptic potentials (IPSPs) in VD4 were completely and reversibly blocked by sevoflurane (4%). Sevoflurane also suppressed action potentials in both RPeD1 and VD4 cells. To determine whether the anesthetic-induced synaptic depression involved postsynaptic transmitter receptors, dopamine was pressure applied to VD4, either in the presence or absence of sevoflurane. Dopamine (10−]5 M) activated a voltage-insensitive K+ current in VD4. The same K+ current was also altered by sevoflurane; however, the effects of two compounds were nonadditive. Because transmitter release from RPeD1 requires Ca2+ influx through voltage-gated Ca2+ channels, we next tested whether the anesthetic-induced synaptic depression involved these channels. Individually isolated RPeD1 somata were whole cell voltage clamped, and Ca2+ currents were analyzed in control and various anesthetic conditions. Clinically relevant concentrations of sevoflurane did not significantly affect voltage-activated Ca2+ channels in RPeD1. Taken together, this study provides the first direct evidence that sevoflurane-induced synaptic depression involves both pre- and postsynaptic ion channels.

Halothane-induced synaptic depression at both in vivo and in vitro reconstructed synapses between identified Lymnaea neurons

1995 ◽  
Vol 74 (6) ◽  
pp. 2604-2613 ◽  
Author(s):  
G. E. Spencer ◽  
N. I. Syed ◽  
K. Lukowiak ◽  
W. Winlow
Keyword(s):  
Synaptic Transmission ◽  
Lymnaea Stagnalis ◽  
Cell Types ◽  
Inhibitory Synapses ◽  
General Anesthetics ◽  
General Anesthetic ◽  
Presynaptic Neuron ◽  
Novel Approach

1. In the present study we tested the ability of the general anesthetic, halothane, to affect synaptic transmission at in vivo and in vitro reconstructed peptidergic synapses between identified neurons of Lymnaea stagnalis. 2. An identified respiratory interneuron, visceral dorsal 4 (VD4), innervates a number of postsynaptic cells in the central ring ganglia of Lymnaea. Because VD4 has previously been shown to exhibit immunoreactivity for FMRFamide-related peptides, it was hypothesized that these peptides may be utilized by VD4 during synaptic transmission. In the intact, isolated CNS of Lymnaea, we have identified novel connections between VD4 and the pedal A (PeA) cells. We demonstrate that VD4 makes inhibitory connections with the PeA neurons, in particular PeA4, and that these synaptic responses are mimicked by exogenous application of FMRFamide. 3. The synaptic transmission between VD4 and the PeA cells in an intact, isolated CNS preparation was completely blocked in 2%, but not 1% halothanc. Interestingly, the postsynaptic responses (PeA) to exogenous FMRFamide were maintained in the presence of both 1 and 2% halothane. 4. To determine the specificity of the observed responses and to determine the precise synaptic site of anesthetic action, we reconstructed the VD4/PeA synapses in vitro. After isolation from their respective ganglia, both cell types extended processes and established neuritic contact. We demonstrated that not only did the presynaptic neuron reestablish the appropriate inhibitory synapses with the PeA neurons, but that the PeA cells also maintained their responsiveness to exogenous FMRFamide. 5. Superfusion of the in vitro synaptically connected VD4 and PeA cells with 2% halothane completely abolished the synaptic transmission between these cells. However, even higher concentrations of 4% halothane failed to block the responsiveness of the PeA neurons to exogenous FMRFamide. Moreover, both 1 and 2% halothane enhanced the duration of the postsynaptic response to exogenously applied FMRFamide. These data suggest that the halothane-induced depression of synaptic transmission most likely occurred at the presynaptic level. 6. This study provides the first direct evidence that peptidergic transmission in the nervous system may also be susceptible to the actions of general anesthetics. In addition, we utilized a novel approach of in vitro reconstructed synapses for studying the effects of general anesthetics on monosynaptic transmission in the absence of other synaptic influences.

Substance P stimulates inhibitory synaptic transmission in the guinea pig basolateral amygdala in vitro

2001 ◽  
Vol 40 (6) ◽  
pp. 806-817 ◽  
Author(s):  
Karen A Maubach ◽  
Karine Martin ◽  
David W Smith ◽  
Louise Hewson ◽  
Robert A Frankshun ◽  
...  
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Synaptic Transmission ◽  
Basolateral Amygdala ◽  
Inhibitory Synaptic Transmission

Synaptic integrative properties at hyperbaric pressure

1988 ◽  
Vol 60 (4) ◽  
pp. 1497-1512 ◽  
Author(s):  
Y. Grossman ◽  
J. J. Kendig
Keyword(s):  
Synaptic Transmission ◽  
Motor Neurons ◽  
Repetitive Stimulation ◽  
Inhibitory Synapses ◽  
Synaptic Connections ◽  
Paired Pulse ◽  
Inhibitory Transmission ◽  
Inhibitory Synaptic Transmission ◽  
Hyperbaric Pressure ◽  
Per Se

1. Because hyperbaric pressure profoundly depresses excitatory synaptic transmission, it has proved difficult to account for its excitatory effects in the CNS. We tested the hypothesis that hyperbaric pressure might increase excitation by enhancing facilitation and potentiation during repetitive synaptic activation, and/or by selectively depressing inhibitory synaptic transmission. Intracellular microelectrode recordings were obtained from crustacean muscle fibers innervated by single identifiable excitor and inhibitor motor neurons; the preparations were exposed to pressures of 0.1-10.1 MPa. 2. Hyperbaric pressure reduced the amplitude of the singly evoked excitatory junctional potential (EJP), enhanced paired-pulse facilitation, and increased the potentiation elicited by trains of stimuli. The potentiated EJP at 10.1 MPa approached the comparable response evoked at normobaric pressure. 3. Hyperbaric pressure also depressed inhibitory synaptic transmission, measured as depression of the EJP by the inhibitor motor neuron. However, pressure depressed excitatory and inhibitory synaptic transmission to the same extent. Thus there appears to be no selective effect of pressure on the GABA-activated chloride channel. The amplitude of the inhibited EJP at 10.1 MPa remained below that at normobaric pressure, even during repetitive stimulation. 4. The results do not support the hypothesis that pressure increases central excitation by selectively depressing inhibitory transmission per se; enhancement of potentiation, however, probably plays an important role. In this preparation, in which inhibitory transmission also displays facilitation, pressure did not increase overall excitation or alter the balance between excitation and inhibition. 5. These results predict that a pressure-excitable network should encompass excitatory synaptic connections which exhibit pronounced facilitation and inhibitory synapses with little or no facilitation.

scholarly journals Dementia Enhances Inhibitory Actions of General Anesthetics in Hippocampal Synaptic Transmission

2011 ◽  
Vol 2011 ◽  
pp. 1-5
Author(s):  
Masana Yamada ◽  
Rika Sasaki ◽  
Koki Hirota ◽  
Mitsuaki Yamazaki
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Gaba Release ◽  
Recurrent Inhibition ◽  
General Anesthetics ◽  
Presynaptic Terminals ◽  
Loss Of Righting Reflex ◽  
Healthy Control

In order to investigate whether dementia modifies the anesthetic actions in the central nervous systems, we have studied effects of general anesthetics on the hippocampal synaptic transmission using the dementia model mice. Preliminary in vivo experiments revealed that time of loss of righting reflex following sevoflurane inhalation was more shortened in dementia mice than in healthy control mice. Field population spikes of hippocampal CA1 pyramidal neurons were elicited in vitro using orthodromic stimulation of Schaffer collateral commissural fibers (test pulse). The recurrent inhibition was enhanced with the second stimulating electrode placed in alveus hippocampi (prepulse) to activate recurrent inhibition of CA1. The prepulses were applied as train stimuli to activate release and then deplete γ-amino-butyric acid (GABA) at presynaptic terminals of inhibitory interneurons. Sevoflurane and thiopental had greater actions on inhibitory synaptic transmission in dementia model mice than in control mice. The pre-pulse train protocol revealed that the anesthetic-induced GABA discharge was more enhanced in dementia mice than in control mice. Dementia enhances the actions of general anesthetics due to the increase in GABA release from presynaptic terminals.

scholarly journals Deletion of PLCγ1 in GABAergic neurons increases seizure susceptibility in aged mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hye Yun Kim ◽  
Yong Ryoul Yang ◽  
Hongik Hwang ◽  
Ha-Eun Lee ◽  
Hyun-Jun Jang ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Molecular Mechanisms ◽  
Gabaergic Neurons ◽  
Inhibitory Synapses ◽  
Synaptic Inhibition ◽  
Behavioral Alterations ◽  
Inhibitory Synaptic Transmission ◽  
Aged Mice ◽  
Phospholipase Cγ1 ◽  
Genetic Deletion

AbstractSynaptic inhibition plays a fundamental role in the information processing of neural circuits. It sculpts excitatory signals and prevents hyperexcitability of neurons. Owing to these essential functions, dysregulated synaptic inhibition causes a plethora of neurological disorders, including epilepsy, autism, and schizophrenia. Among these disorders, epilepsy is associated with abnormal hyperexcitability of neurons caused by the deficits of GABAergic neuron or decreased GABAergic inhibition at synapses. Although many antiepileptic drugs are intended to improve GABA-mediated inhibition, the molecular mechanisms of synaptic inhibition regulated by GABAergic neurons are not fully understood. Increasing evidence indicates that phospholipase Cγ1 (PLCγ1) is involved in the generation of seizure, while the causal relationship between PLCγ1 and seizure has not been firmly established yet. Here, we show that genetic deletion of PLCγ1 in GABAergic neurons leads to handling-induced seizure in aged mice. In addition, aged Plcg1F/F; Dlx5/6-Cre mice exhibit other behavioral alterations, including hypoactivity, reduced anxiety, and fear memory deficit. Notably, inhibitory synaptic transmission as well as the number of inhibitory synapses are decreased in the subregions of hippocampus. These findings suggest that PLCγ1 may be a key determinant of maintaining both inhibitory synapses and synaptic transmission, potentially contributing to the regulation of E/I balance in the hippocampus.

scholarly journals Age-dependent actions of dopamine on inhibitory synaptic transmission in superficial layers of mouse prefrontal cortex

2013 ◽  
Vol 109 (5) ◽  
pp. 1323-1332 ◽  
Author(s):  
Kush Paul ◽  
Charles L. Cox
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
D2 Receptor ◽  
Early Time ◽  
Inhibitory Response ◽  
Cellular Level ◽  
Inhibitory Synaptic Transmission ◽  
Time Period

Numerous developmental changes in the nervous system occur during the first several weeks of the rodent lifespan. Therefore, many characteristics of neuronal function described at the cellular level from in vitro slice experiments conducted during this early time period may not generalize to adult ages. We investigated the effect of dopamine (DA) on inhibitory synaptic transmission in superficial layers of the medial prefrontal cortex (PFC) in prepubertal [postnatal age (P; days) 12–20], periadolescent (P30–48), and adult (P70–100) mice. The PFC is associated with higher-level cognitive functions, such as working memory, and is associated with initiation, planning, and execution of actions, as well as motivation and cognition. It is innervated by DA-releasing fibers that arise from the ventral tegmental area. In slices from prepubertal mice, DA produced a biphasic modulation of inhibitory postsynaptic currents (IPSCs) recorded in layer II/ III pyramidal neurons. Activation of D2-like receptors leads to an early suppression of the evoked IPSC, which was followed by a longer-lasting facilitation of the IPSC mediated by D1-like DA receptors. In periadolescent mice, the D2 receptor-mediated early suppression was significantly smaller compared with the prepubertal animals and absent in adult animals. Furthermore, we found significant differences in the DA-mediated lasting enhancement of the inhibitory response among the developmental groups. Our findings suggest that behavioral paradigms that elicit dopaminergic release in the PFC differentially modulate inhibition of excitatory pyramidal neuron output in prepuberty compared with periadolescence and adulthood in the superficial layers (II/III) of the cortex.

scholarly journals Paradoxical excitation of lateral habenula neurons by propofol involves enhanced presynaptic release of glutamate

2021 ◽  
Author(s):  
Ryan David Shepard ◽  
Kunwei Wu ◽  
Wei Lu
Keyword(s):  
Synaptic Transmission ◽  
Neuronal Excitability ◽  
Critical Role ◽  
Cell Voltage ◽  
General Anesthetics ◽  
Physiological Basis ◽  
Lateral Habenula ◽  
Sleep Physiology ◽  
Presynaptic Release ◽  
Synaptic Drive

Sleep is a fundamental physiological process conserved across most species. As such, deficits in sleep can result in a myriad of psychological and physical health issues. However, the mechanisms underlying the induction of sleep are relatively unknown. Interestingly, general anesthetics cause unconsciousness by positively modulating GABA-A receptors (GABAARs). Based on this observation, it is hypothesized that GABAARs play a critical role in modulating circuits involved in sleep to promote unconsciousness. Recently, the lateral habenula (LHb) has been demonstrated to play a role in sleep physiology and sedation. Specifically, propofol has been shown to excite LHb neurons to promote sedation. However, the mechanism by which this occurs is unknown. Here, we utilize whole-cell voltage and current clamp recordings from LHb neurons obtained from 8-10 week old male mice to determine the physiological mechanisms for this phenomenon. We show that bath application of 1.5μM propofol is sufficient to increase LHb neuronal excitability involving synaptic transmission, but not through modulation of intrinsic properties. Additionally, although there is increased LHb neuronal excitability, GABAARs localized postsynaptically on LHb neurons are still responsive to propofol, as indicated by an increase in the decay time. Lastly, we find that propofol increases the synaptic drive onto LHb neurons involving enhanced presynaptic release of both glutamate and GABA. However, the greatest contributor to the potentiated synaptic drive is the increased release of glutamate which shifts the balance of synaptic transmission towards greater excitation. Taken together, this study is the first to identify the physiological basis for why LHb neurons are excited by propofol, rather than inhibited, and as a result promote sedation.

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