Diverse Actions of Astrocytes in GABAergic Signaling

An imbalance of excitatory and inhibitory neurotransmission leading to over excitation plays a crucial role in generating seizures, while enhancing GABAergic mechanisms are critical in terminating seizures. In recent years, it has been reported in many studies that astrocytes are deeply involved in synaptic transmission. Astrocytes form a critical component of the “tripartite” synapses by wrapping around the pre- and post-synaptic elements. From this location, astrocytes are known to greatly influence the dynamics of ions and transmitters in the synaptic cleft. Despite recent extensive research on excitatory tripartite synapses, inhibitory tripartite synapses have received less attention, even though they influence inhibitory synaptic transmission by affecting chloride and GABA concentration dynamics. In this review, we will discuss the diverse actions of astrocytic chloride and GABA homeostasis at GABAergic tripartite synapses. We will then consider the pathophysiological impacts of disturbed GABA homeostasis at the tripartite synapse.

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Faculty Opinions recommendation of Isoflurane-sensitive presynaptic R-type calcium channels contribute to inhibitory synaptic transmission in the rat thalamus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1149894.608949 ◽

2009 ◽

Author(s):

M Bruce MacIver

Keyword(s):

Calcium Channels ◽

Synaptic Transmission ◽

Inhibitory Synaptic Transmission

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Faculty Opinions recommendation of Imbalanced suppression of excitatory and inhibitory synaptic transmission onto mouse striatal projection neurons during induction of anesthesia with sevoflurane in vitro.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717950204.793455454 ◽

2012 ◽

Author(s):

Bernd Antkowiak ◽

Harald Hentschke

Keyword(s):

Synaptic Transmission ◽

Projection Neurons ◽

Inhibitory Synaptic Transmission ◽

Striatal Projection Neurons

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Faculty Opinions recommendation of Optogenetic silencing strategies differ in their effects on inhibitory synaptic transmission.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717953614.793459219 ◽

2012 ◽

Author(s):

Vivien Casagrande ◽

Gopathy Purushothaman

Keyword(s):

Synaptic Transmission ◽

Inhibitory Synaptic Transmission

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Presynaptic actions of propofol enhance inhibitory synaptic transmission in isolated solitary tract nucleus neurons

Brain Research ◽

10.1016/j.brainres.2009.06.058 ◽

2009 ◽

Vol 1286 ◽

pp. 75-83 ◽

Cited By ~ 20

Author(s):

Young-Ho Jin ◽

Zhenxiong Zhang ◽

David Mendelowitz ◽

Michael C. Andresen

Keyword(s):

Synaptic Transmission ◽

Solitary Tract Nucleus ◽

Solitary Tract ◽

Inhibitory Synaptic Transmission

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Wnt signaling pathway improves central inhibitory synaptic transmission in a mouse model of Duchenne muscular dystrophy

Neurobiology of Disease ◽

10.1016/j.nbd.2015.11.018 ◽

2016 ◽

Vol 86 ◽

pp. 109-120 ◽

Cited By ~ 7

Author(s):

Marco Fuenzalida ◽

Claudia Espinoza ◽

Miguel Ángel Pérez ◽

Cheril Tapia-Rojas ◽

Loreto Cuitino ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Mouse Model ◽

Synaptic Transmission ◽

Wnt Signaling ◽

Signaling Pathway ◽

Wnt Signaling Pathway ◽

Inhibitory Synaptic Transmission

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Hemoglobin metabolites mimic benzodiazepines and are possible mediators of hepatic encephalopathy

Blood ◽

10.1182/blood-2003-03-0739 ◽

2003 ◽

Vol 102 (4) ◽

pp. 1525-1528 ◽

Cited By ~ 14

Author(s):

Brian J. Ruscito ◽

Neil L. Harrison

Keyword(s):

Cognitive Impairment ◽

Hepatic Encephalopathy ◽

Synaptic Transmission ◽

Liver Failure ◽

Gabaa Receptor ◽

Protoporphyrin Ix ◽

Aminobutyric Acid ◽

Endogenous Ligands ◽

Inhibitory Synaptic Transmission ◽

Clinical Observations

Abstract Liver failure is often accompanied by cognitive impairment and coma, a syndrome known as hepatic encephalopathy (HE). The administration of flumazenil, a benzodiazepine (BZ) antagonist, is effective in reversing the symptoms of HE in many patients. These clinical observations gave rise to notions of an endogenous BZ-like mechanism in HE, but to date no viable candidate compounds have been characterized. We show here that the hemoglobin (Hb) metabolites hemin and protoporphyrin IX (PPIX) interact with the BZ site on the γ-aminobutyric acid (GABAA) receptor and enhance inhibitory synaptic transmission in a manner similar to diazepam and zolpidem. This finding suggests that hemin and PPIX are neuroactive porphyrins capable of acting as endogenous ligands for the central BZ site. The accumulation of these porphyrins under pathophysiologic conditions provides a potentially novel mechanism for the central manifestations of HE.

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Late-onset, short-term intermittent fasting reverses age-related changes in calcium buffering and inhibitory synaptic transmission in mouse basal forebrain neurons

Journal of Neuroscience ◽

10.1523/jneurosci.1442-21.2021 ◽

2021 ◽

pp. JN-RM-1442-21

Author(s):

Eunyoung Bang ◽

Annette S. Fincher ◽

Sophie Nader ◽

David A. Murchison ◽

William H. Griffith

Keyword(s):

Synaptic Transmission ◽

Basal Forebrain ◽

Late Onset ◽

Intermittent Fasting ◽

Short Term ◽

Inhibitory Synaptic Transmission ◽

Age Related ◽

Calcium Buffering ◽

Mouse Basal Forebrain ◽

Age Related Changes

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Rapidly Deactivating AMPA Receptors Determine Excitatory Synaptic Transmission to Interneurons in the Nucleus Tractus Solitarius From Rat

Journal of Neurophysiology ◽

10.1152/jn.1997.78.1.82 ◽

1997 ◽

Vol 78 (1) ◽

pp. 82-91 ◽

Cited By ~ 29

Author(s):

Stefan Titz ◽

Bernhard U. Keller

Keyword(s):

Synaptic Transmission ◽

Ampa Receptor ◽

Decay Time ◽

Ampa Receptors ◽

Time Course ◽

Nucleus Tractus Solitarius ◽

Synaptic Cleft ◽

Excitatory Synaptic Transmission ◽

Membrane Properties ◽

Time Constants

Titz, Stefan and Bernhard U. Keller. Rapidly deactivating AMPA receptors determine excitatory synaptic transmission to interneurons in the nucleus tractus solitarius from rat. J. Neurophysiol. 78: 82–91, 1997. Excitatory synaptic transmission was investigated in interneurons of the parvocellular nucleus tractus solitarius (pNTS) by performing patch-clamp experiments in thin slice preparations from rat brain stem. Stimulation of single afferent fibers evoked excitatory postsynaptic currents (EPSCs) mediated by glutamate receptors of the dl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) and N-methyl-d-aspartate types. AMPA-receptor-mediated EPSCs displayed decay time constants of 3.5 ± 1.2 (SD) ms (13 cells), which were slow compared with EPSC decay time constants in neurons of the cerebellum or hippocampus. Slow EPSC decay was not explained by dendritic filtering, because the passive membrane properties of pNTS interneurons provided favorable voltage-clamp conditions. Also, the slowness of EPSC decay did not result from slow deactivation of AMPA receptors (0.7 ± 0.2 ms, 5 cells), which was investigated during rapid application of agonist to outside-out patches. Comparison of AMPA receptor kinetics with EPSC decay time constants suggested that the slow time course of EPSCs resulted from the prolonged presence of glutamate in the synaptic cleft.

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