From Astrocytic Calcium Signaling to Synaptic Resilience: Emerging Insights in Pathology and Physiology

Astrocytes have historically been viewed as mere supportive cells within the brain, but recent advances have positioned them as central to understanding brain function. This paradigm shift is driven by accumulating experimental evidence that portrays astrocytes not just as supportive but as proactive agents influencing various brain functions, including facilitating synaptic plasticity and neurophysiological mechanisms. The main second messenger for astrocyte function, i.e. calcium (Ca2+), has been the focus of significant research, revealing intricate details about astrocyte signaling pathways. Technological advancements over the past two decades have uncovered the complex and dynamic nature of astrocyte Ca2+ signaling especially within astrocyte Ca2+ microdomains, crucial to both spontaneous and evoked activity. This has spurred interest in the diverse activities and morphologies of astrocytes and their implications in health and disease within the glia research community.



Regarding the relationship between astrocyte morphology and Ca2+ activity, central questions that remain to be addressed are:



• How do morphologically distinct astrocytes influence different types of synapses?



• Can we differentiate astrocytes based on their roles with excitatory versus inhibitory functions?



• In pathological contexts, for instance in neurodegenerative diseases such as Alzheimer’s, how do the prominent changes in astrocyte morphology and Ca2+ signaling affect synaptic plasticity and resilience?



Pathological conditions reveal significant alterations in astrocyte morphology and Ca2+ signaling, which are pivotal in the progression of brain diseases. These changes potentially undermine synaptic plasticity and resilience, yet the exact mechanisms remain poorly understood.



Additionally, emerging research suggests that astrocytes, alongside microglia, can actively participate in phagocytosis within the brain. The extent of this activity, its comparison to microglial activity, and the impact of astrocyte Ca2+ signaling and morphological changes on their phagocytic capabilities require further exploration and clarification through methodological and technical innovations allowing to modulate astrocyte morphology.



This Research Topic welcomes contributions from researchers around the globe in the form of Original Research, Review, Mini Review, and Perspectives focusing on, but not limited to, the following subtopics:



- Variability in astrocyte Ca2+ responses to different neurotransmitters.



- Functional implications of astrocyte heterogeneity across different brain areas.



- Role of astrocytes in phagocytosis and debris clearance, highlighting technical advancements, and discoveries.



- Contributions of astrocytes to synaptic pruning in AD across human and animal model studies.



- Development and application of new tools for modulating astrocyte activity and reactivity.



- Investigating how modulation of astrocyte Ca2+ activity or morphology influences behavioral outcomes.