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

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

Buenos Aires, Argentina.

Congreso; 1er Encuentro del Club de la Glía Cono Sur; 2022

We studied the role of glutamate transporter GLT–1, specifically located in astrocytes, inlearning and memory processes. We used the spatial object recognition (SOR) task in rats tostudy the effect of GLT-1 inhibition. In this task, a strong training session induced long-termmemory (LTM) formation and a weak training session only induced short-term memory butnot LTM. We administered dihydrokainic acid (DHK), a selective GLT-1 inhibitor, in thehippocampus to affect different stages of memory. Our results suggest that DHK has differenteffects when applied either in a strong or a weak SOR training. The hippocampal inhibition ofGLT – 1 promoted LTM formation from a weak training session in a protein-synthesisdependent manner. This effect was dependent on brain-derived neurotrophic factor and theexpression of the activity-regulated cytoskeletal protein, which are plasticity related proteinsnecessary for memory consolidation. Furthermore, DHK impaired memory expression,reconsolidation and persistence, when administered before a test session, after a reactivationsession, or before a second training session, respectively. On the other hand, chronic systemicadministration of Ceftriaxone, which is known to enhance the synthesis of GLT- 1, did notaffect acquisition and short-term memory expression, but impairs LTM formation.These findings reveal that glutamate homeostasis mediated by GLT-1, is a key mechanisminvolved in spatial memory formation and disruption.