Lack of CRH Affects the Behavior but Does Not Affect the Formation of Short-Term Memory

Abstract

Corticotropin-releasing hormone (CRH) is involved in modification of synaptic transmission and affects spatial discrimination learning, i.e., affects the formation of memory in long-term aspect. Therefore, we have focused on CRH effect on short-term memory. We have used stress task avoidance (maze containing three zones: entrance, aversive, and neutral) and compared the behavior and short-term memory in wild-type mice and mice lacking CRH (CRH KO) experiencing one 120-min session of restraint stress. As control, non-stressed animals were used. As expected, the animals that experienced the stress situation tend to spend less time in the zone in which the restraint chamber was present. The animals spent more time in the neutral zone. There were significant differences in number of freezing bouts in the aversive and entrance zones in CRH KO animals. CRH KO control animals entered the neutral zone much more faster than WT control and spent more time immobile in the neutral zone than WT control. These data give evidence that lacking of CRH itself improves the ability of mice to escape away from potentially dangerous area (i.e., those in which the scent of stressed animal is present).

Keywords: CRH; Post-stress period; Restraint stress; Stress task avoidance; Working memory.

Fig. 1

a Stress task avoidance apparatus scheme. Zone 1 aversive zone with restraint chamber; zone 2 entrance zone; zone 3 neutral zone. b Time schedule of experiment. The animals were bred in reversed light/dark regime, i.e., lights of at 6:00 and light on at 18:00. Stress was applied from 14:00 to 16:00 (120 min), i.e., in the dark period that is natural for animal activity and then the animals were tested

Fig. 2

Total distance traveled (top left), number of freezing episodes (top right), and total time for which the animal is immobile (left bottom). WT wild types, KO CRH KO mice, ctrl control, restr animals previously restrained. Significant differences are marked as follows: *p < 0.05

Fig. 3

Number of freezing bouts in aversive zone (top left), in entrance zone (top right), in neutral zone (bottom left) and number of entries to neutral zone (bottom right). WT wild types, KO CRH KO mice, ctrl control, restr animals previously restrained. Significant differences are marked as follows: *p < 0.05, **p < 0.01, ***p < 0.001 (differences between ctrl and restr), ^# p < 0.05 (differences between WT ctrl and KO ctrl)

Fig. 4

Freezing time in neutral zone (top left), time for which the animal is immobile in neutral zone (top right), latency to first entry to neutral zone (middle), number of entries to restraint chamber (bottom left) and time spent in the restraint chamber (bottom right). WT wild types, KO CRH KO mice, ctrl control, restr animals previously restrained. Significant differences are marked as follows: *p < 0.05, **p < 0.01, ***p < 0.001 (differences between ctrl and restr), ^## p < 0.01 (differences between WT ctrl and KO ctrl)