V-060 | GABAergic astrocytic uptake: a key modulator of spatial memory dynamics

Cognition, Behavior, and Memory
Author: Juan Gabriel Riboldi | Email: juangriboldi@gmail.com

Juan Gabriel Riboldi^1°2°3°, Matías Martín Renfijes^1°4°,Josefina Iribarne^1°, Haydee Viola^1°2°3°

^1° CONICET – Universidad de Buenos Aires, Instituto de Biología Celular y Neurociencias “Profesor Eduardo De Robertis” (IBCN), Buenos Aires, Argentina.
^2° Departamento de Fisiología, Biología Molecular y Celular “Dr. Héctor Maldonado” (FBMC), Universidad de Buenos Aires (UBA), Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina.
^3° Instituto Tecnológico de Buenos Aires, Buenos Aires, Argentina.
^4° Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the Central Nervous System, crucial for regulating neuronal excitability. Astrocytes, integral to synaptic function through the tripartite synapse, primarily express GABA transporter 3 (GAT-3), which helps finalize GABA action at the synapse, maintaining neuronal homeostasis. We studied GAT-3 role in spatial memory consolidation, expression, and reconsolidation. We trained rats in spatial object recognition (SOR) task which induces long-term memory and administered SNAP-5114 (SNAP), a GAT-3 inhibitor, into the dorsal hippocampus around the training session. SNAP treatment impaired memory acquisition/consolidation. This impairment was counteracted by prior exposure to an open field (OF) and this improvement was prevented by emetine administration, suggesting that SNAP’s effects on memory consolidation may involve disruptions in protein synthesis. Additionally, Lactacystin, a proteasome inhibitor, mitigated the negative effects of SNAP on memory consolidation when administered before SNAP. Furthermore, SNAP administration before a test session impaired memory expression. However, its infusion before a reactivation session did not impair memory reconsolidation.
These results reveal specific effects of hippocampal GAT-3 blockade on spatial memory, shedding light on GABAergic imbalances from astrocytic dysfunction and their potential role in mental and neurological disorders.