Beyond neurons: involvement of Arc and BDNF on spatial memory stages affected by astroglial glutamate uptake blockage

JUAN G. RIBOLDI; MATIAS RENFIJES; JULIETA CORREA; HAYDEE VIOLA

San Luis, Argentina

Congreso; SAN 2023 XXXVIII Annual Meeting; 2023

Sociedad Argentina de Investigacion en Neurociencias

This study aimed to investigate the role of glutamate transporter GLT–1, located in astrocytes, in spatial memory consolidation, expression, and reconsolidation, along with exploring the cellular mechanisms that occur under GLT-1 blockage. We used the spatial object recognition (SOR) task in rats, and administered dihydrokainic acid (DHK), a selective GLT-1 inhibitor, in the dorsal hippocampus. While a strong training session induced long-term memory (LTM) formation, a weak training session induced short-term memory. Inhibiting GLT-1 around a weak SOR training session promoted SOR-LTM formation. This effect was prevented by the administration of a protein-synthesis inhibitor. Moreover, SOR-LTM promotion by DHK was dependent on hippocampal activity-related cytoskeletal protein (Arc) translation and on brain-derived neurotrophic factor (BDNF) action, plasticity related proteins necessary for memory consolidation. Alternatively, DHK administration before a test session impaired SOR-LTM expression. This effect was prevented if Arc translation was pharmacologically blocked, but not by inhibiting BDNF action. Furthermore, if applied before a reactivation session, DHK impaired reconsolidation and this effect was not reversed by Arc translation inhibition.These findings reveal that hippocampal Arc and BDNF play a pivotal role in spatial memory processes, shedding light on the intricate molecular mechanisms of memory processes, governed by the activity of both neurons and glia.