Maternal attenuation of hypothalamic paraventricular nucleus norepinephrine switches avoidance learning to preference learning in preweanling rat pups

Abstract

Infant rats learn to prefer stimuli paired with pain, presumably due to the importance of learning to prefer the caregiver to receive protection and food. With maturity, a more 'adult-like' learning system emerges that includes the amygdala and avoidance/fear learning. The attachment and 'adult-like' systems appear to co-exist in older pups with maternal presence engaging the attachment system by lowering corticosterone (CORT). Specifically, odor-shock conditioning (11 odor-0.5 mA shock trials) in 12-day-old pups results in an odor aversion, although an odor preference is learned if the mother is present during conditioning. Here, we propose a mechanism to explain pups ability to 'switch' between the dual learning systems by exploring the effect of maternal presence on hypothalamic paraventricular nucleus (PVN) neural activity, norepinephrine (NE) levels and learning. Maternal presence attenuates both PVN neural activity and PVN NE levels during odor-shock conditioning. Intra-PVN NE receptor antagonist infusion blocked the odor aversion learning with maternal absence, while intra-PVN NE receptor agonist infusion permitted odor aversion learning with maternal presence. These data suggest maternal control over pup learning acts through attenuation of PVN NE to reduce the CORT required for pup odor aversion learning. Moreover, these data also represent pups' continued maternal dependence for nursing, while enabling aversion learning outside the nest to prepare for pups future independent living.

Figure 1

Mean (± sem) number of choices toward the conditioned stimulus (CS) odor during the Y-maze test (total of 5 trials) for postsensitive period PN12-15 with or without maternal presence. Asterisk represents a significant difference from each of the other groups (p<0.05). n=5–6.

Figure 2

Mean (± sem) of corticosterone (CORT) levels showed in ng/ml for post-sensitive period PN12 pups comparing animals with maternal presence with animals without maternal presence during odor-shock conditioning. Asterisk represents a significant difference from each of the other groups (p<0.05). n=5–8.

Figure 3

Effect of maternal presence on the 2-DG relative uptake into the parvocellular PVN of postsensitive period pups (PN12-15) during odor-shock conditioning. Bars represent the Mean (± sem) level of 2-DG uptake in the PVN. Asterisk represents a significant difference from all other groups (p<0.05). n=5–7.

Figure 4

(A) Effect of maternal presence on the level of NE into the PVN of postsensitive period pups (PN12-15) during odor-shock conditioning. (B) location of microdialysis probe tips (solid circles) in rats used for NE measurement in the PVN. Asterisk represents a significant difference from all other groups (p<0.05). n=6.

Figure 5

(A) Mean (± SEM) number of choices toward the conditioned stimulus (CS) odor during the Y-Maze test following odor-shock conditioning without maternal presence during NE α1antagonist (prazoxin) infusion directly into the PVN. Asterisks represent significant differences from the control groups (p<0.001) n=5, (B) Mean (± SEM) number of choices toward the conditioned stimulus (CS) odor during the Y-Maze test following odor-shock conditioning with maternal presence during NE α1 agonist (phenylephrine) infusion directly into the PVN. Asterisks represent significant differences from the control groups (p<0.001) n=5, (C) locations of cannula tips (solid circles) in rats used for NE infusion without maternal presence into the PVN, (D) locations of cannula tips (solid circles) in rats used for NE infusion during maternal presence into the PVN, (E) section from a PN12 pup counterstained with cresyl violet and characterizing the extent of H³ NE drug diffusion within the PVN.