Healthy functionality in the brain relies on intricate neuron-glia networks. Recent data suggest that glial, including astrocytes, play a crucial role in the processing and storing on by the brain. In particular, synapses might not be bipartite, but rather tripartite structures, comprised of the pre- and the postsynaptic terminals and the surrounding astrocyte. Moreover, astrocytes, like neurons, form intricate interconnected networks that afford long-range communication via the propagation of calcium waves. Therefore, neurons and astrocytes form intertwined neuron-glial networks supporting active partnership between the two cell populations. Hence, understanding the nature of neuron-glia interactions is essential to understand how the brain functions, and will serve as a stepping stone for deciphering brain disorders.Our long-term goal is to reveal the mechanisms that control and regulates the activity of combined neuron-glia networks. The specific objectives of this application, which are fundamental in the pursuit of that goal, are (1) to determine the properties of astrocytic modulation of synaptic transmission; and (2) to characterize how such modulation shapes neuronal activity in neuron-glia networks of the brain.To pursue these aims we will employ a comprehensive theoretical investigation to develop mathematical and biophysical models in support to experiments, at the many levels and scales of action of neuron-astrocyte signaling.The significance of understanding glia-neuron interactions is several-fold as it pertains to a very wide range of applications, from basic understanding of neuronal activity, to developing therapeutic strategies toward the treatment of neurological disorders. Here, we will focus on how modulations of synaptic transmission by astrocytes could favor the emergence of synchronized neuronal, leveraging the predictions of our theoretical approach in the perspective of brain disorders, and epilepsy in particular.