Here I 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 cue (ref 1). 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 disease (ref 2). Third, I will report a validation work for a new effective, specific and consequential attenuation tool of astrocyte Gq-GPCR signaling in vivo (ref 3). 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 2021