This seminar will report the latest insights on astrocyte signaling in the adult neural circuits, by using multiple integrated approaches, including calcium imaging, electrophysiology, opto/pharmaco-genetics, mouse behavioral tests, RNA-seq and new astrocyte manipulation tools that we recently developed. First, I will describe mechanisms of bi-directional neuron-astrocyte communications in the striatum that lead to hyperactivity and disrupted attention via a synaptogenic cue¹. Second, I will present how astrocytes respond to distinct perturbations and how we can use the molecular signaling information for phenotypic benefits in neurodegenerative disease mouse models, e.g. Huntington’s disease². Third, I will report a validation work for a new effective, specific and consequential attenuation tool of astrocyte Gq-GPCR signaling in vivo³. Taken together, our findings show that signaling from astrocytes to neurons is sufficient per se to alter synapses, circuits and behavior. We also provide new tools to study such astrocyte-neuron dynamics.
References:
1.    Nagai J et al., Hyperactivity with disrupted attention by activation of an astrocyte synaptogenic cue. Cell 2019
2.    Yu X and Nagai J et al., Context-specific striatal astrocyte molecular responses are phenotypically exploitable. Neuron 2020
3.    Nagai J et al., Specific and behaviorally consequential astrocyte Gq GPCR signaling attenuation in vivo with ibARK. Neuron in press