Contrasting hippocampal and amygdalar expression of genes related to neural plasticity during escape from social aggression

Abstract

Social subjugation has widespread consequences affecting behavior and underlying neural systems. We hypothesized that individual differences in stress responsiveness were associated with differential expression of neurotrophin associated genes within the hippocampus and amygdala. To do this we examined the brains of hamsters placed in resident/intruder interactions, modified by the opportunity to escape from aggression. In the amygdala, aggressive social interaction stimulated increased BDNF receptor TrK(B) mRNA levels regardless of the ability to escape the aggressor. In contrast, the availability of escape limited the elevation of GluR(1) AMPA subunit mRNA. In the hippocampal CA(1), the glucocorticoid stress hormone, cortisol, was negatively correlated with BDNF and TrK(B) gene expression, but showed a positive correlation with BDNF expression in the DG. Latency to escape the aggressor was also negatively correlated with CA(1) BDNF expression. In contrast, the relationship between amygdalar TrK(B) and GluR(1) was positive with respect to escape latency. These results suggest that an interplay of stress and neurotrophic systems influences learned escape behavior. Animals which escape faster seem to have a more robust neurotrophic profile in the hippocampus, with the opposite of this pattern in the amygdala. We propose that changes in the equilibrium of hippocampal and amygdalar learning result in differing behavioral stress coping choices.

Fig. 1

A schematic of the apparatus for testing social aggression and escape. These behavioral procedures took place in the home cage (20×33×13 cm) of a large aggressive male, fitted with dividers. One divider separated the test animal from the resident, prior to the social interaction (dotted line). The other divider provided an escape route large enough for only the test animal to pass through.

Fig. 2

(A) Latency to escape rapidly decreased and remained significantly less than day 1 for the duration of training and on test day. (B) The presence of an escape hole significantly increased the amount of time it took for the test animal to make contact with the resident. (C) The number of attacks received did not differ between groups. While Aggression Only animals experienced elevated attacks on day 1 (*), the attacks on Escapers were elevated for the first 2 days (+). (D) Training significantly (*, compared to all other days, α, compared to days 3–6, +, compared to day 6) decreased the proportion of time the test animal spent in contact with the aggressor for both the groups that had access to an escape hole (black dots) and those which did not (gray triangles). Hamsters that had access to an escape hole (Escapers) spent a significantly (#) larger portion of the interaction in contact with the aggressor, compared to animals that did not (Aggression Only). α, *, +, # P<0.05.

Fig. 3

Hamsters that had access to an escape hole (Escapers) had a significant correlation in the CA₁ between cortisol and both (A) BDNF and (B) TrK_B mRNA expressions. (C) Cortisol and BDNF were also significantly correlated in the DG.

Fig. 4

Hamsters showed a (A) significant (*P<0.05) negative correlation between BDNF mRNA expression in the CA₁ and the latency to escape on test day 7, and (B) significant differences in BDNF expression between fast (<110 s; N = 6) and slow (>150 s; N = 3) escapers.

Fig. 5

A social interaction was enough to induce a significant (*P<0.05) increase in amygdalar TRK_B mRNA expression relative to the Novel Cage only group (A). Furthermore, there was a significant positive correlation between TRK_B mRNA expression and latency to escape on test day 7 (B). Only the presence of aggression with no opportunity to escape (Aggression Only) induced a significant increase in amygdalar AMPA subunit GluR₁ mRNA expression relative to Novel Cage controls (C). There was a significant positive correlation between GluR₁ mRNA expression and latency to escape on test day 7 (D).