Effects of 17β-estradiol on glutamate synaptic transmission and neuronal excitability in the rat medial vestibular nuclei

Anesthetics appear to produce neurodepression by altering synaptic transmission and/or intrinsic neuronal excitability. Propofol, a widely used anesthetic, has proposed effects on many targets, ranging from sodium channels to GABAA inhibition. We examined effects of propofol on the intrinsic excitability of hippocampal CA1 neurons (primarily interneurons) recorded from adult rat brain slices. Propofol strongly depressed action potential production induced by DC injection, synaptic stimulation, or high-potassium solutions. Propofol-induced depression of intrinsic excitability was completely reversed by bicuculline and picrotoxin but was strychnine-insensitive, implicating GABAA but not glycine receptors. Propofol strongly enhanced inhibitory postsynaptic currents (IPSCs) and induced a tonic GABAA-mediated current. We pharmacologically differentiated tonic and phasic (synaptic) GABAA-mediated inhibition using the GABAA receptor antagonist SR95531 (gabazine). Gabazine (20 μM) completely blocked both evoked and spontaneous IPSCs but failed to block the propofol-induced depression of intrinsic excitability, implicating tonic, but not phasic, GABAA inhibition. Glutamatergic synaptic responses were not altered by propofol (≤30 μM). Similar results were found in both interneurons and pyramidal cells and with the chemically unrelated anesthetic thiopental. These results suggest that suppression of CA1 neuron intrinsic excitability, by these anesthetics, is largely due to activation of tonic GABAA conductances; although other sites of action may play important roles in affecting synaptic transmission, which also can produce strong neurodepression. We propose that for some anesthetics, suppression of intrinsic excitability, mediated by tonic GABAA conductances, operates in conjunction with effects on synaptic transmission, mediated by other mechanisms, to depress hippocampal function during anesthesia.

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Control of motor coordination by astrocytic tonic GABA release through modulation of excitation/inhibition balance in cerebellum

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1721187115 ◽

2018 ◽

Vol 115 (19) ◽

pp. 5004-5009 ◽

Cited By ~ 22

Author(s):

Junsung Woo ◽

Joo Ok Min ◽

Dae-Si Kang ◽

Yoo Sung Kim ◽

Guk Hwa Jung ◽

...

Keyword(s):

Synaptic Transmission ◽

Motor Performance ◽

Neuronal Excitability ◽

Motor Coordination ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Gaba Release ◽

In Vivo Microdialysis ◽

Tonic Inhibition

Tonic inhibition in the brain is mediated through an activation of extrasynaptic GABAA receptors by the tonically released GABA, resulting in a persistent GABAergic inhibitory action. It is one of the key regulators for neuronal excitability, exerting a powerful action on excitation/inhibition balance. We have previously reported that astrocytic GABA, synthesized by monoamine oxidase B (MAOB), mediates tonic inhibition via GABA-permeable bestrophin 1 (Best1) channel in the cerebellum. However, the role of astrocytic GABA in regulating neuronal excitability, synaptic transmission, and cerebellar brain function has remained elusive. Here, we report that a reduction of tonic GABA release by genetic removal or pharmacological inhibition of Best1 or MAOB caused an enhanced neuronal excitability in cerebellar granule cells (GCs), synaptic transmission at the parallel fiber-Purkinje cell (PF-PC) synapses, and motor performance on the rotarod test, whereas an augmentation of tonic GABA release by astrocyte-specific overexpression of MAOB resulted in a reduced neuronal excitability, synaptic transmission, and motor performance. The bidirectional modulation of astrocytic GABA by genetic alteration of Best1 or MAOB was confirmed by immunostaining and in vivo microdialysis. These findings indicate that astrocytes are the key player in motor coordination through tonic GABA release by modulating neuronal excitability and could be a good therapeutic target for various movement and psychiatric disorders, which show a disturbed excitation/inhibition balance.

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Influence of sex and estrous cycle on synaptic responses of the medial vestibular nuclei in rats: Role of circulating 17β-estradiol

Brain Research Bulletin ◽

10.1016/j.brainresbull.2011.11.008 ◽

2012 ◽

Vol 87 (2-3) ◽

pp. 319-327 ◽

Cited By ~ 14

Author(s):

Silvarosa Grassi ◽

Adele Frondaroli ◽

Mariangela Scarduzio ◽

Cristina V. Dieni ◽

Gabriele Brecchia ◽

...

Keyword(s):

Estrous Cycle ◽

Vestibular Nuclei ◽

17Β Estradiol ◽

Synaptic Responses

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Chemokine CCL2 modulation of neuronal excitability and synaptic transmission in rat hippocampal slices

Journal of Neurochemistry ◽

10.1111/j.1471-4159.2010.07121.x ◽

2010 ◽

Vol 116 (3) ◽

pp. 406-414 ◽

Cited By ~ 65

Author(s):

Yan Zhou ◽

Hongmei Tang ◽

Jianuo Liu ◽

Jun Dong ◽

Huangui Xiong

Keyword(s):

Synaptic Transmission ◽

Neuronal Excitability ◽

Hippocampal Slices

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Modulatory effects of the novel TrkB receptor agonist 7,8-dihydroxyflavone on synaptic transmission and intrinsic neuronal excitability in mouse visual cortex in vitro

European Journal of Pharmacology ◽

10.1016/j.ejphar.2013.03.044 ◽

2013 ◽

Vol 709 (1-3) ◽

pp. 64-71 ◽

Cited By ~ 6

Author(s):

Daniele Marongiu ◽

Barbara Imbrosci ◽

Thomas Mittmann

Keyword(s):

Visual Cortex ◽

Synaptic Transmission ◽

Receptor Agonist ◽

Neuronal Excitability ◽

The Novel ◽

Trkb Receptor ◽

Mouse Visual Cortex

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A dialogue between glia and neurons in the retina: modulation of neuronal excitability

Neuron Glia Biology ◽

10.1017/s1740925x0500013x ◽

2004 ◽

Vol 1 (3) ◽

pp. 245-252 ◽

Cited By ~ 26

Author(s):

ERIC A. NEWMAN

Keyword(s):

Synaptic Transmission ◽

Glial Cells ◽

Neuronal Excitability ◽

Ganglion Cells ◽

Brain Slices ◽

Müller Cells ◽

Muller Cells ◽

Signaling Mechanisms ◽

Bidirectional Signaling ◽

Stimulation Of

Bidirectional signaling between neurons and glial cells has been demonstrated in brain slices and is believed to mediate glial modulation of synaptic transmission in the CNS. Our laboratory has characterized similar neuron–glia signaling in the mammalian retina. We find that light-evoked neuronal activity elicits Ca2+ increases in Müller cells, which are specialized retinal glial cells. Neuron to glia signaling is likely mediated by the release of ATP from neurons and is potentiated by adenosine. Glia to neuron signaling has also been observed and is mediated by several mechanisms. Stimulation of glial cells can result in either facilitation or depression of synaptic transmission. Release of D-serine from Müller cells might also potentiate NMDA receptor transmission. Müller cells directly inhibit ganglion cells by releasing ATP, which, following hydrolysis to adenosine, activates neuronal A1 receptors. The existence of bidirectional signaling mechanisms indicates that glial cells participate in information processing in the retina.

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