ASTROCYTIC EXOCYTOSIS: MOLECULAR MECHANISMS UNDERLYING COGNITIVE FUNCTION AND NEURONAL SYNCHRONIZATION

Astrocytes are now recognized as dynamic partners in brain function, actively participating in neuronal communication and metabolism. Exocytosis from astrocytes plays a crucial role in the release of gliotransmitters, including glutamate, ATP, and D-serine, which modulate synaptic strength, synchronize neuronal activity, and regulate synaptic plasticity. Recent research has highlighted the importance of astrocytic exocytosis in higher cognitive functions, including learning, memory formation, and sleep regulation. The dnSNARE mouse model, which enables selective inhibition of astrocytic vesicular release, has been instrumental in elucidating these functions. Our laboratory showed that blocking SNARE-dependent gliotransmitter release from astrocytes using the dnSNARE mouse model desynchronized theta oscillations between the hippocampus and prefrontal cortex and impaired performance on working memory tasks, highlighting the importance of astrocyte signaling in cognitive functions.
To elucidate the molecular underpinnings of this cognitive impairment, we conducted microarray analysis of hippocampal tissue from dnSNARE mice. Our transcriptomic analysis focused on identifying enriched pathways, potential upstream regulators, and disease associations, providing insights into the broader implications of disrupted astrocytic exocytosis on brain function and pathology.