Astrocytes convert network excitation to tonic inhibition of neurons

Héja, László; Nyitrai, Gabriella; Kékesi, Orsolya; Dobolyi, Árpád; Szabó, Pál; Fiáth, Richárd; Ulbert, István; Pál-Szenthe, Borbála; Palkovits, Miklós; Kardos, Julianna

doi:10.1186/1741-7007-10-26

Cited by 138 publications

(167 citation statements)

References 86 publications

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“…These authors found that transient receptor potential A1 channels (TRPA1) Under certain conditions, GATs can reverse their function to release GABA in the extracellular space. In two separate studies, Heja et al [79,80] found that astrocytes convert excitation to tonic inhibition of neurons in hippocampal slices and in in vivo experiments. In the presence of reduced Mg 2þ to increase network activity, they show that glutamate uptake is coupled to the reversal of GAT2/GAT3 that induces a GABA tonic current.…”

Section: Astrocytes Activated By Non-gabaergic Signals Modulate Gabaementioning

confidence: 99%

GABAergic interneuron to astrocyte signalling: a neglected form of cell communication in the brain

Losi

Mariotti

Carmignoto

2014

Phil. Trans. R. Soc. B

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GABAergic interneurons represent a minority of all cortical neurons and yet they efficiently control neural network activities in all brain areas. In parallel, glial cell astrocytes exert a broad control of brain tissue homeostasis and metabolism, modulate synaptic transmission and contribute to brain information processing in a dynamic interaction with neurons that is finely regulated in time and space. As most studies have focused on glutamatergic neurons and excitatory transmission, our knowledge of functional interactions between GABAergic interneurons and astrocytes is largely defective. Here, we critically discuss the currently available literature that hints at a potential relevance of this specific signalling in brain function. Astrocytes can respond to GABA through different mechanisms that include GABA receptors and transporters. GABA-activated astrocytes can, in turn, modulate local neuronal activity by releasing gliotransmitters including glutamate and ATP. In addition, astrocyte activation by different signals can modulate GABAergic neurotransmission. Full clarification of the reciprocal signalling between different GABAergic interneurons and astrocytes will improve our understanding of brain network complexity and has the potential to unveil novel therapeutic strategies for brain disorders. BackgroundOur knowledge of how the brain computes incoming sensory signals and governs our cognitive and motor functions has faced an exponential increase in the last decades. This was made possible thanks to a number of technological advances in molecular biology, brain imaging and optogenetics. It is now clear that the complexity of brain activity relies on fast dynamic interactions between different cell types that are finely and constantly regulated in time and space. The greatest challenge for neuroscientists is represented by the speed, the number and the heterogeneity of cellular signals that relentlessly occur in our brain. Over the last years our understanding of the functional role of two heterogeneous cell populations, i.e. GABAergic interneurons and astrocytic glial cells, has been marked by a significant improvement. Whether and how these cell types interact with each other and what functional significance such a signalling may have in the brain network remain, however, largely undefined.Astrocytes are the major class of glial cells in the brain and play essential roles in brain homeostasis and metabolism. They are coupled in a syncytium through gap junctions and exert a homeostatic control of the extracellular space by regulating the pH, the water content and the extracellular concentration of different neurotransmitters and ions. In addition, astrocytes supply neurons with nutrients, trophic factors, cytokines and neuromodulators [1,2], contributing to the neurovascular coupling mechanism [3,4] and to the defensive reaction to tissue insult. Only recently the role of astrocytes has been extended to functions that were once considered an exclusive domain of neurons, such as short-and longterm modul...

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Section: Astrocytes Activated By Non-gabaergic Signals Modulate Gabaementioning

confidence: 99%

GABAergic interneuron to astrocyte signalling: a neglected form of cell communication in the brain

Losi

Mariotti

Carmignoto

2014

Phil. Trans. R. Soc. B

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“…Furthermore, the average immunofluorescence density showed that the synthesis and secretion of GnRH neurons were suppressed in the immune hypothalamus. However, it is unclear by what mechanism thymulin upregulates GnRH in the immune hypothalamus: whether it involves plastic rearrangements of glial-GnRH neurons adhesiveness or the production of growth factors acting via receptors with tyrosine kinase activity remains to be determined (Mullier et al 2010, Heja et al 2012). …”

Section: Figurementioning

confidence: 99%

Effects of GnRH immunization on the reproductive axis and thymulin

Su¹,

Sun²,

Zhou³

et al. 2015

Journal of Endocrinology

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The bidirectional regulation of thymulin in the reproductive-endocrine function of the hypothalamic-pituitary-gonadal (HPG) axis of rats immunized against GnRH remains largely unclear. We explored the alterations in hormones in the HPG axis in immunized rats to dissect the repressive effect of immunization on thymulin, and to clarify the interrelation of reproductive hormones and thymulin in vivo. The results showed that, in the first 2 weeks of booster immunization, thymulin was repressed when reproductive hormones were severely reduced. The self-feedback regulation of thymulin was then stimulated in later immune stages: the rising circulating thymulin upregulated LH and FSH, including GnRH in the hypothalamus, although the levels of those hormones were still significantly lower than in the control groups. In astrocytes, thymulin produced a feedback effect in regulated GnRH neurons. However, in the arcuate nucleus (Arc) and the median eminence (ME), the mediator of astrocytes and other glial cells were also directly affected by reproductive hormones. Thus, in immunized rats, the expression of glial fibrillary acidic protein was distinctly stimulated in the Arc and ME. This study demonstrated that thymulin was downregulated by immunization against GnRH in early stage. Subsequently, the self-feedback regulation was provoked by low circulating thymulin. Thereafter, rising thymulin levels promoted pituitary gonadotropins levels, while acting directly on GnRH neurons, which was mediated by astrocytes in a region-dependent manner in the hypothalamus.

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“…The latter decrease is reversed by a GABA uptake inhibitor, guvacine, which raises ambient GABA. GABA release by astrocytes also increases the gamma oscillation power in hippocampal area CA1 in vivo (9). Intriguingly, in hippocampal slices of animals lacking δ subunitcontaining GABA A receptors (which mediate tonic conductance in many local cell types including interneurons) the average frequency of cholinergically induced gamma oscillations is increased, whereas the oscillation power tends to drop (10).…”

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confidence: 99%

Tonic GABA _A conductance bidirectionally controls interneuron firing pattern and synchronization in the CA3 hippocampal network

Pavlov

Savtchenko

Song

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

106

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The spiking output of interneurons is key for rhythm generation in the brain. However, what controls interneuronal firing remains incompletely understood. Here we combine dynamic clamp experiments with neural network simulations to understand how tonic GABA A conductance regulates the firing pattern of CA3 interneurons. In baseline conditions, tonic GABA A depolarizes these cells, thus exerting an excitatory action while also reducing the excitatory postsynaptic potential (EPSP) amplitude through shunting. As a result, the emergence of weak tonic GABA A conductance transforms the interneuron firing pattern driven by individual EPSPs into a more regular spiking mode determined by the cell intrinsic properties. The increased regularity of spiking parallels stronger synchronization of the local network. With further increases in tonic GABA A conductance the shunting inhibition starts to dominate over excitatory actions and thus moderates interneuronal firing. The remaining spikes tend to follow the timing of suprathreshold EPSPs and thus become less regular again. The latter parallels a weakening in network synchronization. Thus, our observations suggest that tonic GABA A conductance can bidirectionally control brain rhythms through changes in the excitability of interneurons and in the temporal structure of their firing patterns.tonic conductance | extrasynaptic signaling | oscillations

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Astrocytes convert network excitation to tonic inhibition of neurons

Cited by 138 publications

References 86 publications

GABAergic interneuron to astrocyte signalling: a neglected form of cell communication in the brain

GABAergic interneuron to astrocyte signalling: a neglected form of cell communication in the brain

Effects of GnRH immunization on the reproductive axis and thymulin

Tonic GABA _A conductance bidirectionally controls interneuron firing pattern and synchronization in the CA3 hippocampal network

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Astrocytes convert network excitation to tonic inhibition of neurons

Cited by 138 publications

References 86 publications

GABAergic interneuron to astrocyte signalling: a neglected form of cell communication in the brain

GABAergic interneuron to astrocyte signalling: a neglected form of cell communication in the brain

Effects of GnRH immunization on the reproductive axis and thymulin

Tonic GABA A conductance bidirectionally controls interneuron firing pattern and synchronization in the CA3 hippocampal network

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Tonic GABA _A conductance bidirectionally controls interneuron firing pattern and synchronization in the CA3 hippocampal network