GABA release by hippocampal astrocytes

Abstract

Astrocytes can directly influence neuronal activity through the release of various transmitters acting on membrane receptors expressed by neurons. However, in contrast to glutamate and ATP for instance, the release of GABA (γ-amino-butyric acid) by astrocytes is still poorly documented. Here, we used whole-cell recordings in rat acute brain slices and electron microscopy to test whether hippocampal astrocytes release the inhibitory transmitter GABA. We observed that slow transient inhibitory currents due to the activation of GABAA receptors occur spontaneously in principal neurons of the three main hippocampal fields (CA1, CA3, and dentate gyrus). These currents share characteristics with the slow NMDA receptor-mediated currents previously shown to result from astrocytic glutamate release: they occur in the absence of synaptic transmission and have variable kinetics and amplitudes as well as low frequencies. Osmotic pressure reduction, known to enhance transmitter release from astrocytes, similarly increased the frequency of non-synaptic GABA and glutamate currents. Simultaneous occurrence of slow inhibitory and excitatory currents was extremely rare. Yet, electron microscopy examination of immunostained hippocampal sections shows that about 80% of hippocampal astrocytes [positive for glial fibrillary acidic protein (GFAP)] were immunostained for GABA. Our results provide quantitative characteristics of the astrocyte-to-neuron GABAergic signaling. They also suggest that all principal neurons of the hippocampal network are under a dual, excitatory and inhibitory, influence of astrocytes. The relevance of the astrocytic release of GABA, and glutamate, on the physiopathology of the hippocampus remains to be established.

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

“…Notably, astrocytes in the olfactory bulb were able to release both GABA and glutamate to inhibit or activate synchronously groups of specific cell populations, revealing a complex astrocytic modulation of local network activity [87]. A similar dual action of astrocytes was observed in the hippocampus [89]. All in all, these results raise a number of questions on the ultimate effects of astrocytic signalling in local networks.…”

“…In astrocytes, GABA can be degraded by GABA-a-ketoglutaric acid aminotransferase (GABA-T) to glutamine, which is then released and subsequently captured by neurons. Most relevant to the focus of this review is the finding that GABA itself is released by astrocytes in many brain regions, including the olfactory bulb [87], the ventro-basal thalamus [77,88] and the hippocampus [89]. In the olfactory bulb, Kozlov and co-workers reported the first evidence that astrocytic GABA can induce slow outward currents (SOCs) in neurons.…”

“…The mechanism of astrocytic GABA release is unclear. The fact that both in ventro-basal thalamus and hippocampal slices SOCs were increased in number upon hypo-osmotic challenge suggests a release mechanism sensitive to cell volume [88,89]. A different form of GABA release has been described in astrocytes from cerebellar slices [94,95].…”

“…Do glutamatergic SICs and GABAergic SOCs derive from the same activated astrocytes or do they come from different ones? As to the GABA and glutamate release, Le Meur et al [89] suggest that different astrocytes were probably involved because simultaneous SICs and SOCs were extremely rare. It is possible, however, that the same astrocyte may release both GABA and glutamate, but from distinct releasing sites in contact with different synapses.…”

Biophysically based Computational Models of Astrocyte ~ Neuron Coupling and their Functional Significance

“…Their results demonstrate that astrocytes may play a crucial role in spike timing dependent processes with important implications for neurological diseases. Le Meur et al (2012) use whole-cell recordings in rat acute brain slices and electron microscopy to test whether hippocampal astrocytes release the inhibitory transmitter GABA. They observe that slow transient inhibitory currents share characteristics with the slow NMDA receptor-mediated currents shown previously to result from astrocytic glutamate release.…”