Behavioral consequences following AAV mediated hippocampal EAAC1 knockdown

Abstract

The neuronal glutamate transporter EAAC1 (EAAT3) is present in hippocampal neurons to prevent excessive glutamate accumulation. Glutamate receptor-dependent synaptic plasticity is important for learning and memory. The present study investigates behavior associated with blocking the glutamate transporter EAAC1. To manipulate EAAC1 function, rats were intrahippocampally injected with a adeno-associated viral (AAV) vector encoding an EAAC1 antisense mRNA sequence or an AAV empty cassette. Twenty-eight days following surgery, rats were tested in a delayed matching-to-place (DMTP) watermaze task to examine spatial memory, which is hippocampaldependent. Rats treated with EAAC1 antisense exhibited shorter latencies to locate the target platform relative to controls (p < 0.05). These data indicate that microinfusion of AAV encoding EAAC1 antisense significantly altered performance on task involving glutamate transmission and the hippocampus.