S-102
Spatial memory dynamics depends on GAT-3–mediated protein synthesis
Juan Gabriel Riboldi1,2,3, Matías Martín Renfijes2,4, Josefina Iribarne1,2,3, Lionel Muller Igaz5, Diego Moncada, Haydee Viola1,2,3
  1. Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Fisiología, Biología Molecular y Celular "Dr. Héctor Maldonado" (FBMC), Buenos Aires, Argentina.
  2. CONICET - Universidad de Buenos Aires, Instituto de Biología Celular y Neurociencias "Profesor Eduardo De Robertis" (IBCN), Buenos Aires, Argentina.
  3. Instituto Tecnológico de Buenos Aires, Buenos Aires, Argentina.
  4. Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina.
  5. Universidad de Buenos Aires, Facultad de Ciencias Médicas, Departamento de Ciencias Fisiológicas. Grupo de Neurociencias de Sistemas. Buenos Aires, Argentina.
Presenting Author:
Juan Gabriel Riboldi
juangriboldi@gmail.com
Astrocytes are essential components of the tripartite synapse, modulating neuronal communication and plasticity. A key mechanism involves GABA transporter GAT-3, mainly expressed in astrocytes, which terminates GABAergic signaling and preserves homeostasis. Here, we investigated hippocampal GAT-3 in spatial memory dynamics—consolidation, expression, and reconsolidation—using the spatial object recognition (SOR) task in rats. Pharmacological inhibition with SNAP-5114 (SNAP) impaired consolidation. This deficiency was rescued by prior open field (OF) exposure and blocked by the protein synthesis inhibitor emetine, indicating protein synthesis reliance. Pre-treatment with the proteasome inhibitor β-Lactacystin (β-Lacta) also mitigated SNAP-induced deficits. Puromycin incorporation assays confirmed that SNAP reduced hippocampal protein synthesis. Additionally, SNAP before retrieval impaired memory expression, which was restored by OF or β-Lacta. In contrast, SNAP did not affect reconsolidation, a process disrupted instead by a broader GABA transporter blocker: Nipecotic Acid. These findings reveal that astrocytic GAT-3 selectively modulates memory consolidation and expression, but not reconsolidation, through protein synthesis. Thus, GAT-3 emerges as a pivotal astrocytic regulator of memory dynamics and a potential therapeutic target in disorders with altered GABAergic signaling and cognitive decline, such as epilepsy, Alzheimer’s disease, and other neuropsychiatric conditions.