Paradoxical effects of exercise on hippocampal plasticity and cognition in mice with a heterozygous null mutation in the serotonin transporter gene

Abstract

Background and Purpose: Exercise is known to improve cognitive function, but the exact synaptic and cellular mechanisms remain unclear. We investigated the potential role of the serotonin (5-HT) transporter (SERT) in mediating these effects. Experimental Approach: Hippocampal long-term potentiation (LTP) and neurogenesis were measured in standard-housed and exercising (wheel running) wild-type (WT) and SERT heterozygous (HET) mice. We also assessed hippocampal-dependent cognition using the Morris water maze (MWM) and a spatial pattern separation touchscreen task. Key Results: SERT HET mice had impaired hippocampal LTP regardless of the housing conditions. Exercise increased hippocampal neuro..