Maintaining brain function during the ageing is very important for the mental and physical health. Recent studies showed a crucial importance of communication between two major types of brain cells: neurons transmitting electrical signals and glial cells which maintain the wellbeing and function of neurons. Still, the study of age-related changes in the neuron-glia signaling is far from complete.We studied the impact of physiological and pathological ageing on spontaneous and evoked Ca2+-signalling in the astrocytes of mouse neocortex with particular focus on signals mediated by norepinephrine and endocannabinoid receptors. We observed the general trend of increase of astrocytic signaling with brain maturation (up to 6 month) followed by the considerable decrease towards old age (12-24 month). Our preliminary data showed the significant difference in the astrocytic signaling in neocortex of wild-type and AD model mice (line APP/PS1).We have shown previously that cortical astrocytes are capable to release ATP, glutamate and D-Serine by Ca2+-dependent mechanism. Release of gliotransmitters from cortical astrocytes can be activated via various pathways including direct UV-uncaging of intracellular Ca2+ or G-protein coupled receptors, such as α-adrenoreceptors or CB1 receptors. Importantly, release of both ATP and D-Serine from neocortical astrocytes was not observed in brain slice of dnSNARE mice, expressing dominant-negative SNARE domain selectively in astrocytes. We also discovered that astrocyte-derived ATP can facilitate the induction of long-term potentiation of synaptic plasticity in the neocortex. Additional stimulation of astrocytic Ca2+-signalling via norepinephrine and endocannabinoid receptors did not facilitate LTP in the neocortex of dn-SNARE mice. The preliminary results of behavior experiments show that norepinephrine -mediated glial signaling can affect learning and memory.Our recent data have shown that age-related decrease in the astroglial Ca2+ signalling can cause substantial decrease in the release of gliotransmitters.Age-related impairment of gliotransmitter release from cortical astrocytes can compromise astroglial modulation of synaptic transmission in the neocortex and therefore can contribute to the age-related impairment of synaptic plasticity. We have also observed an alteration in the gliotransmitter release and astrocyte-neuron communications in the APP/PS1 mice, as compared to the wild-type littermates of the same age (12-14 months).Combined, our data show that glia-neuron interaction can significantly decline with ageing and this decline in gliotransmission can contribute to age-related cognitive impairment. Also, our results strongly support the physiological relevance of glial exocytosis for glia neuron-communications and brain function.