Figure 1.

Experimental design. (a) Sedentary (Sed) or exercised (EX) mice were given a 3-min acquisition trial (as a subthreshold learning task as shown previously; Stefanko et al, 2009; McQuown et al, 2011), followed immediately with an i.p. injection of sodium butyrate (NaB) or vehicle (veh), and returning all animals to clean home cages without access to running wheels. Twenty-four hours or 7 days later, a 5-min object location memory (OLM) retention test was administered where one object was moved to a novel location. Time spent exploring the identical objects was recorded and a discrimination index (DI) was calculated to determine preference for the object in the novel location. (b) To determine whether a brain-derived neurotrophic factor (BDNF)-dependent mechanism was involved in the enhancement of subthreshold learning, short-interfering RNA (siRNA) against bdnf, or control siRNA, were infused to the hippocampus 2 days before OLM acquisition. Mice were given a 3-min acquisition trial, followed 24 h later by a 5-min OLM retention test. Animals were killed 1 h after the OLM test, and hippocampi were removed for molecular assays.