Assessing the Beclin-1 Knockout: Autophagy, Neurogenesis, and the TUNL Task

Abstract

Autophagy is the intracellular process of isolating, enveloping, and recycling cell matter. Beclin-1 is a protein that acts as a lynchpin in the autophagic process. Animals lacking Beclin-1 are embryonically lethal, and knockout of Beclin-1 causes a reduction in adult hippocampal neurogenesis. The dentate gyrus (DG) is normally home to ongoing neurogenesis, which is thought to mediate pattern separation and memory encoding. First, I test a new protocol for the TUNL task. To assess whether a behavioural phenotype of Beclin-1 nKO is apparent, on the second experiment I compare TUNL performance between WT and KO mice. The new protocol for the TUNL task produces a reliable measure of pattern separation. Beclin-1 nKO reduced DG neurogenesis by 40% compared to WT. No difference between the WT and KO mice in TUNL task performance (pattern separation ability) was found but KO mice had lower activity in the CA1 during the task.