Arc and BDNF mediated effects of hippocampal astrocytic glutamate uptake blockade on spatial memory stages.

Glutamate is involved in fundamental functions, including neuronal plasticity and memory. Astrocytes are integral elements involved in synaptic function, and the GLT-1 transporter possesses a critical role in glutamate uptake. Here, we study the role of GLT-1, specifically located in astrocytes, in the consolidation, expression, reconsolidation and persistence of spatial object recognition memory in rats. Administration of dihydrokainic acid (DHK), a selective GLT-1 inhibitor, into the dorsal hippocampus around a weak training which only induces short-term memory, promotes long-term memory formation. This promotion is prevented by hippocampal administration of protein-synthesis translation inhibitor, blockade of Activity-regulated cytoskeleton-associated protein (Arc) translation or Brain-Derived Neurotrophic Factor (BDNF) action, which are plasticity related proteins necessary for memory consolidation. However, DHK around a strong training, which induces long-term memory, does not affect memory consolidation. Administration of DHK before the test session impairs the expression of long-term memory, and this effect is dependent of Arc translation. Furthermore, DHK impairs reconsolidation if applied before a reactivation session, and this effect is independent of Arc translation. These findings reveal specific consequences on spatial memory stages developed under hippocampal GLT-1 blockade, shedding light on the intricate molecular mechanisms, governed in part for the action of glia.