The K ir 4.1 channel is crucial for the maintenance of the resting membrane potential of glial cells, and it is believed to play a main role in the homeostasis of extracellular potassium. To understand its importance in these two phenomena, we have measured

Fast exchange of extracellular signals between neurons and astrocytes is crucial for synaptic function. Over the last few decades, different pathways of astroglial release of neuroactive substances have been proposed to modulate neurotransmission. However, their involvement in physiological conditions is highly debated. Connexins, the gap junction forming proteins, are highly expressed in astrocytes and have recently been shown to scale synaptic transmission and plasticity. Interestingly, in addition to gap junction channels, the most abundant connexin (Cx) in astrocytes, Cx43, also forms hemichannels. While such channels are mostly active in pathological conditions, they have recently been shown to regulate cognitive function. However, whether astroglial Cx43 hemichannels are active in resting conditions and regulate basal synaptic transmission is unknown. Here we show that in basal conditions Cx43 forms functional hemichannels in astrocytes from mouse hippocampal slices. We furthermore demonstrate that the activity of astroglial Cx43 hemichannels in resting states regulates basal excitatory synaptic transmission of hippocampal CA1 pyramidal cells through ATP signaling. These data reveal Cx43 hemichannels as a novel astroglial release pathway at play in basal conditions, which tunes the moment-to-moment glutamatergic synaptic transmission.

Isoflurane is a widely used anesthetic which safely and reversibly induces deep coma and associated burst suppression (BS) electroencephalographic patterns. Here we investigate possible underlying causes for the state of cortical hyperexcitability which was recently shown to be one of the characteristics of BS. Our hypothesis was that cortical inhibition is diminished during isoflurane-induced BS. Experiments were performed in vivo using intracellular recordings of cortical neurons to assess their responsiveness to stimulations of connected thalamic nuclei. We demonstrate that during BS EPSPs were diminished by 44%, whereas inhibitory potentials were completely suppressed. This finding was supported by additional results indicating that a decrease in neuronal input resistance normally found during inhibitory responses under low isoflurane conditions was abolished in the BS condition. Moreover, removal of inhibition occasionally revealed excitatory components which were absent during recordings before the induction of BS. We also show that the absence of inhibition during BS is not caused by a blockage of GABA receptors, since iontophoretically applied GABA shows receptor availability. Moreover, the concentration of extracellular chloride was increased during BS, as would be expected after reduced flow of chloride through GABA A receptors. Also inhibitory responses were reinstated by selective blockage of glial glutamate transporters with dihydrokainate. These results suggest that the lack of inhibition during BS is caused by reduced excitation, probably resulting from increased glial uptake of glutamate stimulated by isoflurane, which creates a diminished activation of cortical interneurons. Thus cortical hyperexcitability during BS is favored by suppressed inhibition.

A major breakthrough in neuroscience has been the realization in the last decades that the dogmatic view of astroglial cells as being merely fostering and buffering elements of the nervous system is simplistic. A wealth of investigations now shows that astrocytes actually participate in the control of synaptic transmission in an active manner. This was first hinted by the intimate contacts glial processes make with neurons, particularly at the synaptic level, and evidenced using electrophysiological and calcium imaging techniques. Calcium imaging has provided critical evidence demonstrating that astrocytic regulation of synaptic efficacy is not a passive phenomenon. However, given that cellular activation is not only represented by calcium signaling, it is also crucial to assess concomitant mechanisms. We and others have used electrophysiological techniques to simultaneously record neuronal and astrocytic activity, thus enabling the study of multiple ionic currents and in depth investigation of neuro-glial dialogues. In the current review, we focus on the input such approach has provided in the understanding of astrocyte-neuron interactions underlying control of synaptic efficacy.