scholarly journals Influences of Morphine on the Spontaneous and Evoked Excitatory Postsynaptic Currents in Lateral Amygdala of Rats

2016 ◽  
pp. 165-169 ◽  
Author(s):  
J.-J. ZHANG ◽  
X.-D. LIU ◽  
L.-C. YU
Keyword(s):  
Synaptic Transmission ◽  
Excitatory Synaptic Transmission ◽  
Morphine Treatment ◽  
Lateral Amygdala ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Whole Cell Patch Clamp ◽  
The Central Nervous System ◽  
Underlying Mechanisms

Acute morphine exposure induces antinociceptive activity, but the underlying mechanisms in the central nervous system are unclear. Using whole-cell patch clamp recordings, we explore the role of morphine in the modulation of excitatory synaptic transmission in lateral amygdala neurons of rats. The results demonstrate that perfusion of 10 μM of morphine to the lateral amygdala inhibits the discharge frequency significantly. We further find that there are no significant influences of morphine on the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). Interestingly, morphine shows no marked influence on the evoked excitatory postsynaptic currents (eEPSCs) in the lateral amygdala neurons. These results indicate that acute morphine treatment plays an important role in the modulation on the excitatory synaptic transmission in lateral amygdala neurons of rats.

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.

scholarly journals Infectious disease-associated encephalopathies

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Maria C. Barbosa-Silva ◽  
Maiara N. Lima ◽  
Denise Battaglini ◽  
Chiara Robba ◽  
Paolo Pelosi ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Cognitive Deficits ◽  
Brain Function ◽  
Cell Activation ◽  
Therapeutic Strategies ◽  
Barrier Dysfunction ◽  
Glial Cell Activation ◽  
The Central Nervous System ◽  
Underlying Mechanisms

AbstractInfectious diseases may affect brain function and cause encephalopathy even when the pathogen does not directly infect the central nervous system, known as infectious disease-associated encephalopathy. The systemic inflammatory process may result in neuroinflammation, with glial cell activation and increased levels of cytokines, reduced neurotrophic factors, blood–brain barrier dysfunction, neurotransmitter metabolism imbalances, and neurotoxicity, and behavioral and cognitive impairments often occur in the late course. Even though infectious disease-associated encephalopathies may cause devastating neurologic and cognitive deficits, the concept of infectious disease-associated encephalopathies is still under-investigated; knowledge of the underlying mechanisms, which may be distinct from those of encephalopathies of non-infectious cause, is still limited. In this review, we focus on the pathophysiology of encephalopathies associated with peripheral (sepsis, malaria, influenza, and COVID-19), emerging therapeutic strategies, and the role of neuroinflammation. Graphic abstract

scholarly journals Mice With Monoallelic GNAO1 Loss Exhibit Reduced Inhibitory Synaptic Input To Cerebellar Purkinje Cells

2021 ◽  
Author(s):  
Huijie Feng ◽  
Yukun Yuan ◽  
Michael R Williams ◽  
Alex Roy ◽  
Jeffrey Leipprandt ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Purkinje Cells ◽  
Gabab Receptor ◽  
Molecular Layer ◽  
Loss Of Function ◽  
Whole Cell Patch Clamp ◽  
The Difference ◽  
G Protein Alpha Subunit ◽  
Cerebellar Purkinje Cells

GNAO1 encodes Gαo, a heterotrimeric G protein alpha subunit in the Gi/o family. In this report, we used a Gnao1 mouse model G203R previously described as a gain-of-function Gnao1 mutant with movement abnormalities and enhanced seizure susceptibility. Here, we report an unexpected second mutation resulting in a loss-of-function Gαo protein and describe alterations in central synaptic transmission. Whole cell patch clamp recordings from Purkinje cells (PCs) in acute cerebellar slices from Gnao1 mutant mice showed significantly lower frequencies of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) compared to WT mice. There was no significant change in sEPSCs or mEPSCs. Whereas mIPSC frequency was reduced, mIPSC amplitudes were not affected, suggesting a presynaptic mechanism of action. A modest decrease in the number of molecular layer interneurons was insufficient to explain the magnitude of IPSC suppression. Paradoxically, Gi/o inhibitors (pertussis toxin), enhanced the mutant-suppressed mIPSC frequency and eliminated the difference between WT and Gnao1 mice. While GABAB receptor regulates mIPSCs, neither agonists nor antagonists of this receptor altered function in the mutant mouse PCs. This study is the first electrophysiological investigation of the role of Gi/o protein in cerebellar synaptic transmission using an animal model with a loss-of-function Gi/o protein.

Kainate receptor-mediated synaptic transmissions in the adult rodent insular cortex

2012 ◽  
Vol 108 (7) ◽  
pp. 1988-1998 ◽  
Author(s):  
Kohei Koga ◽  
Su-Eon Sim ◽  
Tao Chen ◽  
Long-Jun Wu ◽  
Bong-Kiun Kaang ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Receptor Antagonist ◽  
Ampa Receptor ◽  
Time Course ◽  
Insular Cortex ◽  
Nmda Receptor Antagonist ◽  
Functional Roles ◽  
Adult Rat ◽  
Whole Cell Patch Clamp ◽  
The Central Nervous System

Kainate (KA) receptors are expressed widely in the central nervous system and regulate both excitatory and inhibitory synaptic transmission. KA receptors play important roles in fear memory, anxiety, and pain. However, little is known about their function in synaptic transmission in the insular cortex (IC), a critical region for taste, memory, and pain. Using whole cell patch-clamp recordings, we have shown that KA receptors contribute to fast synaptic transmission in neurons in all layers of the IC. In the presence of the GABAA receptor antagonist picrotoxin, the NMDA receptor antagonist AP-5, and the selective AMPA receptor antagonist GYKI 53655, KA receptor-mediated excitatory postsynaptic currents (KA EPSCs) were revealed. We found that KA EPSCs are ∼5–10% of AMPA/KA EPSCs in all layers of the adult mouse IC. Similar results were found in adult rat IC. KA EPSCs had a significantly slower rise time course and decay time constant compared with AMPA receptor-mediated EPSCs. High-frequency repetitive stimulations at 200 Hz significantly facilitated the summation of KA EPSCs. In addition, genetic deletion of GluK1 or GluK2 subunit partially reduced postsynaptic KA EPSCs, and exposure of GluK2 knockout mice to the selective GluK1 antagonist UBP 302 could significantly reduce the KA EPSCs. These data suggest that both GluK1 and GluK2 play functional roles in the IC. Our study may provide the synaptic basis for the physiology and pathology of KA receptors in the IC-related functions.

AMPA receptors undergo channel arrest in the anoxic turtle cortex

2008 ◽  
Vol 294 (2) ◽  
pp. R606-R613 ◽  
Author(s):  
Matthew Edward Pamenter ◽  
Damian Seung-Ho Shin ◽  
Leslie Thomas Buck
Keyword(s):  
Cell Death ◽  
Ampa Receptors ◽  
Painted Turtle ◽  
Anoxia Tolerance ◽  
Excitatory Postsynaptic Currents ◽  
Channel Arrest ◽  
Postsynaptic Currents ◽  
Aspartate Receptor ◽  
Excitotoxic Cell Death

Without oxygen, all mammals suffer neuronal injury and excitotoxic cell death mediated by overactivation of the glutamatergic N-methyl-d-aspartate receptor (NMDAR). The western painted turtle can survive anoxia for months, and downregulation of NMDAR activity is thought to be neuroprotective during anoxia. NMDAR activity is related to the activity of another glutamate receptor, the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR). AMPAR blockade is neuroprotective against anoxic insult in mammals, but the role of AMPARs in the turtle's anoxia tolerance has not been investigated. To determine whether AMPAR activity changes during hypoxia or anoxia in the turtle cortex, whole cell AMPAR currents, AMPAR-mediated excitatory postsynaptic potentials (EPSPs), and excitatory postsynaptic currents (EPSCs) were measured. The effect of AMPAR blockade on normoxic and anoxic NMDAR currents was also examined. During 60 min of normoxia, evoked peak AMPAR currents and the frequencies and amplitudes of EPSPs and EPSCs did not change. During anoxic perfusion, evoked AMPAR peak currents decreased 59.2 ± 5.5 and 60.2 ± 3.5% at 20 and 40 min, respectively. EPSP frequency (EPSPƒ) and amplitude decreased 28.7 ± 6.4% and 13.2 ± 1.7%, respectively, and EPSCƒ and amplitude decreased 50.7 ± 5.1% and 51.3 ± 4.7%, respectively. In contrast, hypoxic (Po2 = 5%) AMPAR peak currents were potentiated 56.6 ± 20.5 and 54.6 ± 15.8% at 20 and 40 min, respectively. All changes were reversed by reoxygenation. AMPAR currents and EPSPs were abolished by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In neurons pretreated with CNQX, anoxic NMDAR currents were reversibly depressed by 49.8 ± 7.9%. These data suggest that AMPARs may undergo channel arrest in the anoxic turtle cortex.

scholarly journals Mycobacterium abscessuscording prevents phagocytosis and promotes abscess formation

2014 ◽  
Vol 111 (10) ◽  
pp. E943-E952 ◽  
Author(s):  
Audrey Bernut ◽  
Jean-Louis Herrmann ◽  
Karima Kissa ◽  
Jean-François Dubremetz ◽  
Jean-Louis Gaillard ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Wide Spectrum ◽  
Mycobacterium Abscessus ◽  
Abscess Formation ◽  
Zebrafish Embryos ◽  
Clinical Syndromes ◽  
The Central Nervous System ◽  
Underlying Mechanisms

Mycobacterium abscessusis a rapidly growingMycobacteriumcausing a wide spectrum of clinical syndromes. It now is recognized as a pulmonary pathogen to which cystic fibrosis patients have a particular susceptibility. TheM. abscessusrough (R) variant, devoid of cell-surface glycopeptidolipids (GPLs), causes more severe clinical disease than the smooth (S) variant, but the underlying mechanisms of R-variant virulence remain obscure. Exploiting the optical transparency of zebrafish embryos, we observed that the increased virulence of theM. abscessusR variant compared with the S variant correlated with the loss of GPL production. The virulence of the R variant involved the massive production of serpentine cords, absent during S-variant infection, and the cords initiated abscess formation leading to rapid larval death. Cording occurred within the vasculature and was highly pronounced in the central nervous system (CNS). It appears thatM. abscessusis transported to the CNS within macrophages. The release ofM. abscessusfrom apoptotic macrophages initiated the formation of cords that grew too large to be phagocytized by macrophages or neutrophils. This study is a description of the crucial role of cording in the in vivo physiopathology ofM. abscessusinfection and emphasizes cording as a mechanism of immune evasion.

Mechanisms Shaping Fast Excitatory Postsynaptic Currents in the Central Nervous System

2002 ◽  
Vol 14 (1) ◽  
pp. 1-19 ◽  
Author(s):  
Mladen I. Glavinović
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ampa Receptors ◽  
Time Course ◽  
Basic Element ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Theoretical Investigations ◽  
The Central Nervous System ◽  
New Hypothesis

How different factors contribute to determine the time course of the basic element of fast glutamate-mediated excitatory postsynaptic currents (mEPSCs) in the central nervous system has been a focus of interest of neurobiologists for some years. In spite of intensive investigations, these mechanisms are not well understood. In this review, basic hypotheses are summarized, and a new hypothesis is proposed, which holds that desensitization of AMPA receptros plays a major role in shaping the time course of fast mEPSCs. According to the new hypothesis, desensitization shortens the time course of mEPSCs largely by reducing the buffering of glutamate molecules by AMPA receptors. The hypothesis accounts for numerous findings on fast mEPSCs and is expected to be equally fruitful as a framework for further experimental and theoretical investigations.

scholarly journals TRPV1 channels contribute to spontaneous glutamate release in nucleus tractus solitarii following chronic intermittent hypoxia

2019 ◽  
Vol 121 (3) ◽  
pp. 881-892 ◽  
Author(s):  
David D. Kline ◽  
Sheng Wang ◽  
Diana L. Kunze
Keyword(s):  
Synaptic Transmission ◽  
Intermittent Hypoxia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Nucleus Tractus Solitarii ◽  
Chronic Intermittent Hypoxia ◽  
Excitatory Postsynaptic Currents ◽  
Epsc Amplitude ◽  
Postsynaptic Currents ◽  
Transient Receptor

Chronic intermittent hypoxia (CIH) reduces afferent-evoked excitatory postsynaptic currents (EPSCs) but enhances basal spontaneous (s) and asynchronous (a) EPSCs in second-order neurons of nucleus tractus solitarii (nTS), a major area for cardiorespiratory control. The net result is an increase in synaptic transmission. The mechanisms by which this occurs are unknown. The N-type calcium channel and transient receptor potential cation channel TRPV1 play prominent roles in nTS sEPSCs and aEPSCs. The functional role of these channels in CIH-mediated afferent-evoked EPSC, sEPSC, and aEPSC was tested in rat nTS slices following antagonist inhibition and in mouse nTS slices that lack TRPV1. Block of N-type channels decreased aEPSCs in normoxic and, to a lesser extent, CIH-exposed rats. sEPSCs examined in the presence of TTX (miniature EPSCs) were also decreased by N-type block in normoxic but not CIH-exposed rats. Antagonist inhibition of TRPV1 reduced the normoxic and the CIH-mediated increase in sEPSCs, aEPSCs, and mEPSCs. As in rats, in TRPV1+/+ control mice, aEPSCs, sEPSCs, and mEPSCs were enhanced following CIH. However, none were enhanced in TRPV1−/− null mice. Normoxic tractus solitarii (TS)-evoked EPSC amplitude, and the decrease after CIH, were comparable in control and null mice. In rats, TRPV1 was localized in the nodose-petrosal ganglia (NPG) and their central branches. CIH did not alter TRPV1 mRNA but increased its protein in NPG consistent with an increased contribution of TRPV1. Together, our studies indicate TRPV1 contributes to the CIH increase in aEPSCs and mEPSCs, but the CIH reduction in TS-EPSC amplitude occurs via an alternative mechanism. NEW & NOTEWORTHY This study provides information on the underlying mechanisms responsible for the chronic intermittent hypoxia (CIH) increase in synaptic transmission that leads to exaggerated sympathetic nervous and respiratory activity at baseline and in response to low oxygen. We demonstrate that the CIH increase in asynchronous and spontaneous excitatory postsynaptic currents (EPSCs) and miniature EPSCs, but not decrease in afferent-driven EPSCs, is dependent on transient receptor potential vanilloid type 1 (TRPV1). Thus TRPV1 is important in controlling nucleus tractus solitarii synaptic activity during CIH.

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