Communication between neuronal and glial cells is regarded to be very important for brain functions such as memory and cognition and many brain pathologies like ischemia, epilepsy and Alzheimer disease. Astrocytes enwrap neurons and therefore are exposed to various neurotransmitters spilled out of synaptic cleft. In response, astrocytes can release of gliotransmitters, such as D-serine, glutamate and ATP, and modulate synaptic strength and signalling within neuronal networks. Extracellular ATP can acts as neurotransmitter mediating the excitatory synaptic transmission in the central nervous system. More importantly, ATP can also mediate the signal transfer between neuronal and glial circuits and within glial networks. ATP released from glial cells can modulate synaptic plasticity and development of neural cells and contribute to various pathological processes. These effects of ATP are mediated by ionotropic P2X and metabotropic P2Y receptors abundantly expressed in many types of neurons and glial cells. There is growing evidence that release of gliotransmitters, including ATP, from the astrocytes shares the common mechanisms of vesicular neurotransmitter release, such as dependence on the proton gradient, SNARE proteins and intracellular Ca2+ elevation. Physiological role of ATP release from astrocytes was suggested by the data on participation of ATP in propagation of glial Ca2+-waves and significant contribution of purines to the astroglia-driven modulation of neuronal activity. Still, most of the evidence of Ca2+-dependent exocytosis of gliotransmitters has been provided by in vitro experiments using astrocytes in culture thus casting doubts on the functional importance of this mechanism in situ and in vivo. Traditionally, the major role in activation of Ca2+-dependent gliotransmitter release was suggested for the metabotorpic P2Y receptors, abundantly expressed in astrocytes. The role for metabotropic Ca2+ signalling was questionned recently when experiments on genetically modified mice with altered InsP3/Ca2+ cascade found that neither enhancement not inhibition of astroglial metabotropic Ca2+ signalling affects synaptic transmission in hippocampus. So, the mechanism of glial exocytosis of ATP and other gliotransmitters and its importance for regulation of neuron signalling in situ and in vivo remain controversial. The results of our recent experiments in neocortical astrocytes and neurons could help to resolve these controversies. Firstly, we have shown that cortical astrocytes express functional ionotropic receptors to ATP, composed mainly from P2X1 and P2X5 subunits. Astroglial P2X1/5 receptors exhibit very high affinity to ATP and, together with astroglial NMDA receptors, mediate fast glial synaptic currents (GSCs) triggered in the cortical astrocytes in response to stimulation of neuronal afferents. Astroglial P2X1/5 receptors have considerable Ca2+ permeability and their activation triggered robust transient Ca2+ signals in the cortical astrocytes. We have also found that maturation and ageing of the brain of mice (from 1 to 20 months) affected the purinergic signaling in cortical astrocytes: the density of P2X receptors and ATP-mediated component of Ca2+-signalling are smallest in young, maximal in adult and once more decrease in the aged mice. Secondly, we have demonstrated that vesicular release of ATP from cortical astrocytes can be activated via various pathways including Ca2+-permeable ionotropic astroglial receptors or direct UV-uncaging of intracellular Ca2+. We have not observed release of ATP from astrocytes of dnSNARE transgenic mice in which the SNARE-dependent exocytosis was selectively impaired in astroglial cells. We have also found out that release of ATP from the neocortical astrocytes caused considerable decrease in the amplitude of both synaptic and tonic inhibitory currents in the cortical pyramidal neurons. This effect was mediated by phosphorylation of GABAA receptors activated by Ca2+-entry through the neuronal P2 purinoreceptors. Furthermore, modulation of neuronal inhibition by astrocyte-driven ATP affected the induction of long-term synaptic plasticity in the neocortex. Both release of ATP from astrocytes and its modulatory effects on synaptic transmission were eliminated in dnSNARE mice. These findings demonstrate an importance of SNARE complex-dependent exocytosis of ATP for glia-neuron interaction in the neocortex. Our results show a novel pathway of glia-neuron communication involving vesicular release of ATP from astrocytes and interaction between P2 and GABA receptors. Our data also imply that ATP-mediated communication between astrocytes and neurons in the neocortex undergoes remodeling during brain ageing and decrease in the ATP release from astrocytes may contribute to the age-related impairment of synaptic plasticity.