Glutamate Released from Glial Cells Synchronizes Neuronal Activity in the Hippocampus

The unconventional N-methyl-d-aspartate (NMDA) receptor subunits GluN3A and GluN3B can, when associated with the other glycine-binding subunit GluN1, generate excitatory conductances purely activated by glycine. However, functional GluN1/GluN3 receptors have not been identified in native adult tissues. We discovered that GluN1/GluN3A receptors are operational in neurons of the mouse adult medial habenula (MHb), an epithalamic area controlling aversive physiological states. In the absence of glycinergic neuronal specializations in the MHb, glial cells tuned neuronal activity via GluN1/GluN3A receptors. Reducing GluN1/GluN3A receptor levels in the MHb prevented place-aversion conditioning. Our study extends the physiological and behavioral implications of glycine by demonstrating its control of negatively valued emotional associations via excitatory glycinergic NMDA receptors.

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Osmotic regulation of neuronal activity: a new role for taurine and glial cells in a hypothalamic neuroendocrine structure

Progress in Neurobiology ◽

10.1016/s0301-0082(99)00071-4 ◽

2000 ◽

Vol 62 (2) ◽

pp. 113-134 ◽

Cited By ~ 136

Author(s):

Nicolas Hussy ◽

Charlotte Deleuze ◽

Michel G. Desarménien ◽

Françoise C. Moos

Keyword(s):

Glial Cells ◽

Neuronal Activity ◽

Osmotic Regulation

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Glial cell regulation of neuronal activity and blood flow in the retina by release of gliotransmitters

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2014.0195 ◽

2015 ◽

Vol 370 (1672) ◽

pp. 20140195 ◽

Cited By ~ 72

Author(s):

Eric A. Newman

Keyword(s):

Blood Flow ◽

Arachidonic Acid ◽

Glial Cells ◽

Neuronal Activity ◽

Neurovascular Coupling ◽

Müller Cells ◽

Future Research ◽

Prostaglandin E ◽

Sk Channels ◽

Muller Cells

Astrocytes in the brain release transmitters that actively modulate neuronal excitability and synaptic efficacy. Astrocytes also release vasoactive agents that contribute to neurovascular coupling. As reviewed in this article, Müller cells, the principal retinal glial cells, modulate neuronal activity and blood flow in the retina. Stimulated Müller cells release ATP which, following its conversion to adenosine by ectoenzymes, hyperpolarizes retinal ganglion cells by activation of A1 adenosine receptors. This results in the opening of G protein-coupled inwardly rectifying potassium (GIRK) channels and small conductance Ca 2+ -activated K + (SK) channels. Tonic release of ATP also contributes to the generation of tone in the retinal vasculature by activation of P2X receptors on vascular smooth muscle cells. Vascular tone is lost when glial cells are poisoned with the gliotoxin fluorocitrate. The glial release of vasoactive metabolites of arachidonic acid, including prostaglandin E 2 (PGE 2 ) and epoxyeicosatrienoic acids (EETs), contributes to neurovascular coupling in the retina. Neurovascular coupling is reduced when neuronal stimulation of glial cells is interrupted and when the synthesis of arachidonic acid metabolites is blocked. Neurovascular coupling is compromised in diabetic retinopathy owing to the loss of glial-mediated vasodilation. This loss can be reversed by inhibiting inducible nitric oxide synthase. It is likely that future research will reveal additional important functions of the release of transmitters from glial cells.

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Photoinactivation of the giant neuropil glial cells in the leech Hirudo medicinalis: effects on neuronal activity and synaptic transmission

Journal of Neurophysiology ◽

10.1152/jn.1996.76.5.2861 ◽

1996 ◽

Vol 76 (5) ◽

pp. 2861-2871 ◽

Cited By ~ 6

Author(s):

J. Schmidt ◽

J. W. Deitmer

Keyword(s):

Synaptic Transmission ◽

Glial Cells ◽

Neuronal Activity ◽

Lucifer Yellow ◽

Hirudo Medicinalis ◽

Membrane Properties ◽

Sensory Cells ◽

Chemical Synapse ◽

Segmental Ganglion ◽

Retzius Cells

1. We studied the effects of photoinactivation of neuropil glial (NG) cells of the leech Hirudo medicinalis on neuronal activity and synaptic transmission. Each segmental ganglion contains two of these giant glial cells, which are electrically and dye coupled. 2. One of the two NG cells in an isolated segmental ganglion was filled with the dye Lucifer yellow (LY). Subsequent irradiation of the ganglion with laser light (440 nm) to photolyze LY caused irreversible depolarization of both NG cells. The NG cells that were filled with LY depolarized from -73 +/- 1.1 (SE) mV to -22 +/- 2.4 mV within 25 +/- 2.8 min of continuous irradiation (n = 22). The other NG cell, which was not directly filled with LY, depolarized with some delay. 3. Photoinactivation of the NG cells caused an irreversible depolarization of Retzius neurons and noxious (N) sensory cells by a mean of 14 mV (n = 36) and 9 mV (n = 24), respectively. In addition, the input resistance was reduced by 54% in Retzius cells and by 34% in N cells. Spikes could not be evoked in Retzius cells after the inactivation of the NG cells, either by intracellular current injection or by electrical nerve stimulation. Similarly, anterior pagoda neurons, annulus erector neurons, and the excitor neurons of the ventrolateral circular muscles became inexcitable. However, N cells, heart interneurons, and most of the heart motor neurons, touch cells, and pressure cells could still generate spontaneous or evoked action potentials. 4. Photoinactivation of the NG cells impaired the electrical connection between the two Retzius neurons. The electrical coupling was completely eliminated in six of eight cell pairs and reduced by 66% in two others. 5. Photoinactivation of the NG cells in the 3rd and 4th segmental ganglion caused a complete block of the chemical synapse between reciprocal inhibitory heart interneurons in these ganglia; the bursting rhythm either stopped or changed to a tonic activity, whereas inhibitory postsynaptic potentials could not be recorded in either heart interneuron anymore. 6. Laser irradiation alone had no effect on neuronal activity and synaptic transmission. Addition of glutathione (10 mM) and ascorbic acid (10 mM) to the saline to bind extracellular radicals that might be produced by the irradiation did not suppress the effects caused by photoinactivation of NG cells. 7. Elevation of bath K+ concentration to 12 mM, acidification of the saline to pH 5.5, and alkalinization to pH 8.5 for 6 min each did not mimick the effects on membrane properties of Retzius cells as produced by inactivation of NG cells. The results suggest some role of glial cells in the maintenance of neuronal activity and electrical and chemical synaptic transmission.

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Spiral Intercellular Calcium Waves in Hippocampal Slice Cultures

Journal of Neurophysiology ◽

10.1152/jn.1998.79.2.1045 ◽

1998 ◽

Vol 79 (2) ◽

pp. 1045-1052 ◽

Cited By ~ 96

Author(s):

Marni E. Harris-White ◽

Stephen A. Zanotti ◽

Sally A. Frautschy ◽

Andrew C. Charles

Keyword(s):

Calcium Signaling ◽

Glial Cells ◽

Neuronal Activity ◽

Hippocampal Slice ◽

Excitable Medium ◽

Calcium Waves ◽

Organotypic Cultures ◽

Hippocampal Slice Cultures ◽

Stratum Oriens ◽

Bath Application

Harris-White, Marni E., Stephen A. Zanotti, Sally A. Frautschy, and Andrew C. Charles. Spiral intercellular calcium waves in hippocampal slice cultures. J. Neurophysiol. 79: 1045–1052, 1998. Complex patterns of intercellular calcium signaling occur in the CA1 and CA2 regions of hippocampal slice organotypic cultures from neonatal mice. Spontaneous localized intercellular Ca2+ waves involving 5–15 cells propagate concentrically from multiple foci in the stratum oriens and s. radiatum. In these same regions, extensive Ca2+ waves involving hundreds of cells propagate as curvilinear and spiral wavefronts across broad areas of CA1 and CA2. Ca2+ waves travel at rates of 5–10 μm/s, are abolished by thapsigargin, and do not require extracellular Ca2+. Staining for astrocytes and neurons indicates that these intercellular waves occur primarily in astrocytes. The frequency and amplitude of Ca2+ waves increase in response to bath application of N-methyl-d-aspartate (NMDA) and decrease in response to removal of extracellular Ca2+ or application of tetrodotoxin. This novel pattern of intercellular Ca2+ signaling is characteristic of the behavior of an excitable medium. Networks of glial cells in the hippocampus may behave as an excitable medium whose spatial and temporal signaling properties are modulated by neuronal activity.

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Astrocytes and Behavior

Annual Review of Neuroscience ◽

10.1146/annurev-neuro-101920-112225 ◽

2021 ◽

Vol 44 (1) ◽

Author(s):

Paulo Kofuji ◽

Alfonso Araque

Keyword(s):

Glial Cells ◽

Neuronal Activity ◽

Animal Behavior ◽

Paradigm Shift ◽

Mammalian Brain ◽

Annual Review ◽

Publication Date ◽

Brain Circuits ◽

Intracellular Ca ◽

And Behavior

Animal behavior was classically considered to be determined exclusively by neuronal activity, whereas surrounding glial cells such as astrocytes played only supportive roles. However, astrocytes are as numerous as neurons in the mammalian brain, and current findings indicate a chemically based dialog between astrocytes and neurons. Activation of astrocytes by synaptically released neurotransmitters converges on regulating intracellular Ca2+ in astrocytes, which then can regulate the efficacy of near and distant tripartite synapses at diverse timescales through gliotransmitter release. Here, we discuss recent evidence on how diverse behaviors are impacted by this dialog. These recent findings support a paradigm shift in neuroscience, in which animal behavior does not result exclusively from neuronal activity but from the coordinated activity of both astrocytes and neurons. Decoding how astrocytes and neurons interact with each other in various brain circuits will be fundamental to fully understanding how behaviors originate and become dysregulated in disease. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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