Astrocytic glutamate uptake as a key mechanism involved in spatial memory formation and disruption

JUAN G. RIBOLDI; JULIETA CORREA; MATIAS RENFIJES; PABLO BUDRIESI; RAMIRO TINTORELLI; HAYDEE VIOLA

Buenos Aires, Argentina.

Congreso; SAN 2022 XXXVII Annual Meeting; 2022

Sociedad Argentina de Investigacion en Neurociencias

The objective of this work was to study the role of Glutamate transporter GLT-1, specifically located in astrocytes, in learning and memory processes. Here, we used the spatial object recognition (SOR) task in rats to study the effect of GLT-1 inhibition. In this task, a strong training session induced long-term memory (LTM) formation and a weak training session only induced short-term memory (STM) but not LTM. We administered dihydrokainic acid (DHK), a selective GLT-1 inhibitor, in the hippocampus to affect different stages of memory. Our results suggest that DHK has different effects when applied either in a strong or a weak SOR training. The inhibition of GLT-1 promoted LTM formation from a weak training session in a protein-synthesis dependent manner. This effect was dependent on brain-derived neurotrophic factor and the expression of the activity-regulated cytoskeletal protein, which are plasticity related proteins necessary for memory consolidation. Furthermore, DHK impaired memory expression, reconsolidation and persistence, when administered before a test session, after a reactivation session, or before a second training session, respectively. On the other hand, chronic systemic administration of Ceftriaxone, which is known to enhance the synthesis of GLT-1, did not affect acquisition and STM expression, but impairs LTM formation. These findings reveal that glutamate homeostasis mediated by GLT-1, is a key mechanism involved in memory formation and disruption.