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

Abstract

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...

Computational Astrocyence: Astrocytes encode inhibitory activity into the frequency and spatial extent of their calcium elevations

“…The neurotransmitter receptors of astrocytes in this study are the GABA receptors (GABARs). Astrocytes have both metabotropic (GABA B Rs) and ionotropic (GABA A Rs) receptors [21]. Although there is some controversy about which type of receptors gives rise to Ca 2+ elevations in astrocytes [22], an increasing amount of evidence suggests that the slower and spatially expanded Ca 2+ waves are induced by GABA B Rs [6].…”

Alterations of Astrocytes in the Context of Schizophrenic Dementia

“…GABA acts on astrocytes through GABA receptors, contributing to the release of chlorine and depolarization of astrocytes, and GABA receptors, activating calcium-dependent mechanisms and contributing to the growth of gliotransmitter (glutamate, ATP, cytokines) (Losi et al, 2014;Rossi, 2015). Activation of presynaptic GABA receptors increases the inhibitory effects of interneurons.…”

Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states

“…Neither GABA nor VIP appeared to exert significant direct vascular effects in vivo that could account for the haemodynamic response [49], stressing GABA's role in inducing changes in cortical activity that then transduce haemodynamic signals. Similar to glutamate, GABA can activate astrocytes, in particular by triggering Ca 2þ events, but whether GABA-A or GABA-B receptors mediate these effects remains a matter of debate [126]. The exact role of astroglial messengers and Ca 2þ increases in NVC also remains unclear [127], and it was recently challenged regarding the exact nature of the glutamate receptors involved [128,129], in particular mGluR5, due to their age-dependent expression [129] and the timing and extent of their contribution [130][131][132].…”