Autoimmune inflammation triggers aberrant astrocytic calcium signaling to impair synaptic plasticity

Abstract Cortical pathology involving inflammatory and neurodegenerative mechanisms is a hallmark of multiple sclerosis and a correlate of disease progression and cognitive decline. Astrocytes play a pivotal role in multiple sclerosis initiation and progression but astrocyte-neuronal network alterations contributing to gray matter pathology remain undefined. Here we unveil deregulation of astrocytic calcium signaling and astrocyte-to-neuron communication as key pathophysiological mechanisms of cortical dysfunction in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Using two-photon imaging ex vivo and fiber