Ablation of the Presynaptic Protein Mover Impairs Learning Performance and Decreases Anxiety Behavior in Mice

Abstract

The presynaptic protein Mover/TPRGL/SVAP30 is absent in Drosophila and C. elegans and differentially expressed in synapses in the rodent brain, suggesting that it confers specific functions to subtypes of presynaptic terminals. In order to investigate how the absence of this protein affects behavior and learning, Mover knockout mice (KO) were subjected to a series of established learning tests. To determine possible behavioral and cognitive alterations, male and female 8-week-old KO and C57Bl/6J wildtype (WT) control mice were tested in a battery of memory and anxiety tests. Testing included the cross maze, novel object recognition test (NOR), the Morris water maze (MWM), the elevated plus maze (EPM), and the open field test (OF). Mover KO mice showed impaired recognition memory in the NOR test, and decreased anxiety behavior in the OF and the EPM. Mover KO did not lead to changes in working memory in the cross maze or spatial reference memory in the MWM. However, a detailed analysis of the swimming strategies demonstrated allocentric-specific memory deficits in male KO mice. Our data indicate that Mover appears to control synaptic properties associated with specific forms of memory formation and behavior, suggesting that it has a modulatory role in synaptic transmission.

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“…The elevated plus maze (EPM) was used to assess anxietyrelated and exploratory behavior (Himanshu et al 2020;Kraeuter et al 2019). The apparatus was made of four arms (5 cm width × 15 cm length) extending at 90° angles from a central area (5 cm width × 5 cm length) raised 75 cm above a padded surface (Schleicher et al 2022).…”

“…Distance traveled and the time spent in each arm were recorded using the ANY-Maze tracking software (Stoelting Co, Wood Dale, IL, USA). Anxiety-like behavior was calculated based on the time spent in the open arms, with longer times spent in the open arms corresponding to lower levels of anxiety (Schleicher et al 2022). After each mouse the EPM was cleaned using 70% ethanol to eliminate odor cues.…”

“…In order to assess recognition memory and novelty preference (Antunes and Biala 2012), the novel object recognition test (NOR) was performed in an open-field arena made of gray plastic (50 × 50 cm) as previously described (Schleicher et al 2022). Twenty-four hours after the Open field test, NOR was performed in the same arena containing two identical objects.…”

“…In order to assess spatial reference memory, the Morris water maze test was used as described before (Bouter et al 2018;Schleicher et al 2022). Briefly, the test relies on spatial cues to locate a submerged hidden platform (10 cm diameter) in a circular pool (110 cm diameter) filled with non-transparent tap water.…”

“…During the acquisition training proximal visual cues were attached to the outside of the pool and the flag was removed from the platform. The platform location remained stationary throughout training and mice were introduced into the pool from one of four predefined entry points (Schleicher et al 2022).…”