Exploring Astrocyte-Neuron interactions with 2-Photon Laser Scanning Microscopy (2PLSM) and Liquid Chromatography-Mass Spectrometry (LCMS) to unveil new therapeutic targets for Autism Spectrum Disorder

Human brain is composed of 80÷100 billion neurons and a similar number of astrocytes, the main non neuronal cell population. Astrocytes, together with microglia, regulate brain tissue development, metabolism, homeostasis and take place in the defensive response in case of infections or injuries, playing a crucial role in neuroinflammation, a common condition in several brain disorders. More recently it was shown that astrocytes actively take place in brain information processing, once considered an exclusively neuronal function. Astrocytes indeed modulate neuronal synaptic activity and plasticity, affecting cognitive functions and behavior. A crucial mechanism is represented by intracellular calcium transients in astrocytes and the following release of different molecules, called gliotransmitters, that modulate neuronal functions. With the advent of genetically encoded calcium indicators and (2PLSM), it is now possible to study Ca²⁺ events that occur in astrocytic thin processes that contact synapses. We use 2PLSM to study Ca²⁺ signals in mice cortical astrocytes in combination with electrophysiological recordings, optogenetics and chemogenetics. Our results show that Ca²⁺ signals in astrocytic processes are dynamic and complex signals that play a crucial role in the modulation of synaptic plasticity and memory retention. In a mouse model of Autism Spectrum Disorder (ASD), we observed altered astrocyte calcium activity in somatosensory cortex, a region relevant to tactile sensory response. Using LCMS, we are now studying a class of endogenous lipidic molecules that may protect brain tissue in conditions of neuroinflammation, reducing or even preventing some symptoms such as behavioral disorders and cognitive impairments. Understanding all the molecular mechanisms involved is crucial to develop new therapeutic tools for neurodevelopmental and other brain disorders.