Neuropsin-dependent and -independent behavioral tagging

Abstract

Aim: The consolidation of short-term memories into long-term memories is promoted by associations with novel environmental stimuli. This phenomenon is known as behavioral tagging. Neuropsin, a plasticity-related serine protease in the hippocampus and amygdala, is involved in memory formation. This study investigated how neuropsin affects associative long-term memory.

Methods: Short-term and long-term memory were assessed in control and neuropsin-deficient mice by investigating their performance in inhibitory avoidance and spatial object recognition tasks. The effect of exposure to novelty on the conversion of short-term memory to associative long-term memory was also examined.

Results: The consolidation of task-related short-term memories into long-term memories was facilitated by exposing the animals to a novel environment 1 hour before training. However, this long-term memory conversion was impaired in neuropsin-deficient mice performing the inhibitory avoidance task but not the spatial object recognition task.

Conclusion: Behavioral tagging occurs via neuropsin-dependent and neuropsin-independent processes for different behavioral tasks.

Keywords: LTM; STM; behavioral tagging; neuropsin.

FIGURE 1

Schematic diagram of experimental procedures. Behavioral tasks were performed individually in all experiments and no mouse preformed multiple tasks. Mice were trained in an IA task with two weak foot shocks (0.1 mA, 100 ms) with a 1 s interval, and then tested for short‐term memory (STM) 15 min later (A) or long‐term memory (LTM) 24 h later (B). Exploration of a novel field (Nov) for 15 min was allowed 1 h before IA training (C). Exploration of a novel field (Nov) for 15 min was allowed 1 h before IA training. Mice received an infusion of recombinant neuropsin (rNP) or vehicle (phosphate‐buffered saline (PBS)) before training (D). Mice received an infusion of recombinant neuropsin (rNP) or vehicle (phosphate‐buffered saline (PBS)) before training, and then tested for LTM 24 h later (E). Mice were trained in a spatial object recognition (SOR) task and then tested for STM (F) or LTM (G). Exploration of a novel field for 15 min was allowed 1 h before SOR training (H)

FIGURE 2

The IA task induces short‐term memory (STM) in wild‐type (WT) and neuropsin‐deficient (NPKO) mice. Mice were trained in an IA task with two weak foot shocks (0.1 mA, 100 ms) with a 1 s interval. Latency to step down from the platform was recorded as a measurement of STM (15 min later). Data are means ± SEMs; *P < .05 by Tukey‐Kramer analysis after two‐way ANOVA

FIGURE 3

Neuropsin (NP) is critical for novelty‐induced long‐term memory (LTM) formation in the IA task. LTM for the IA task was assessed in mice with or without 15 min exposure to a novel field (Nov) 1 h before training. Wild‐type (WT) but not neuropsin‐deficient (NPKO) mice exhibited novelty‐induced LTM consolidation for the IA task. Data are means ± SEMs; **P < .01 by Tukey‐Kramer analysis after two‐way ANOVA

FIGURE 4

Novelty‐induced LTM consolidation was restored in NPKO mice that received brief (5 min) infusions of recombinant NP (rNP; 0.2 μg/ml, 5 min, 0.5 μl/min) before training, but not vehicle (phosphate‐buffered saline (PBS)). Data are means ± SEMs; **P < .01 by Tukey‐Kramer analysis after two‐way ANOVA

FIGURE 5

LTM was not enhanced in NPKO mice that received brief (5 min) infusions of vehicle (phosphate‐buffered saline (PBS)) or recombinant NP (rNP; 0.2 μg/ml, 5 min, 0.5 μl/min) before training. Data are means ± SEMs

FIGURE 6

Spatial object recognition (SOR) training induces short‐term memory (STM) in wild‐type (WT) and neuropsin‐deficient (NPKO) mice. WT and NPKO mice show a preference for the familiar object in a new location after 15 min but not after 24 h. Data are means ± SEMs; *P < .05 by Tukey‐Kramer analysis after two‐way ANOVA

FIGURE 7

Neuropsin (NP) is dispensable for novelty‐induced long‐term memory (LTM) formation in spatial object recognition (SOR) task. Exposure to a novel field for 15 min before training facilitated the formation of LTM in both wild‐type (WT) and NP‐deficient (NPKO) mice. Data are means ± SEMs; *P < .05 and **P < .01 by Tukey‐Kramer analysis after two‐way ANOVA