Increased amygdalar metabotropic glutamate receptor 7 mRNA in a genetic mouse model of impaired fear extinction

Abstract

Rationale: Post-traumatic stress disorder (PTSD) is a devastating anxiety-related disorder which develops subsequent to a severe psychologically traumatic event. Only ~ 9% of people who experience such a trauma develop PTSD. It is clear that a number of factors, including genetics, influence whether an individual will develop PTSD subsequent to a trauma. The 129S1/SvImJ (S1) inbred mouse strain displays poor fear extinction and may be useful to model this specific aspect of PTSD. The metabotropic glutamate receptor 7 (mGlu₇ receptor) has previously been shown to be involved in cognitive processes and anxiety-like behaviour placing it in a key position to regulate fear extinction processes. We sought to compare mGlu₇ receptor mRNA levels in the S1 strain with those in the robustly extinguishing C57BL/6J (B6) inbred strain using in situ hybridisation (ISH) in three brain regions associated with fear extinction: the amygdala, hippocampus and prefrontal cortex (PFC).

Results: Compared to the B6 strain, S1 mice had increased mGlu₇ receptor mRNA levels in the lateral amygdala (LA) and basolateral amygdala (BLA) subdivisions. An increase was also seen in the hippocampal CA1 and CA3 subregions of S1 mice. No difference in mGlu₇ receptor levels were seen in the central nucleus (CeA) of the amygdala, dentate gyrus (DG) of the hippocampus or prefrontal cortex.

Conclusions: These data show altered mGlu₇ receptor expression in key brain regions associated with fear extinction in two different inbred mouse strains which differ markedly in their fear extinction behaviour. Altered mGlu₇ receptor levels may contribute to the deficit fear extinction processes seen in fear extinction in the S1 strain.

Keywords: Post-traumatic stress disorder; Trauma; mGlu7 receptor expression.

Fig. 1

In situ hybridisation of mGlu₇ receptor in the amygdala of B6 and S1 mice. a–c Densitometric analysis showing the S1 mice had increased levels of mGlu₇ receptor in the amygdala (LA + BLA), lateral amygdala (LA) and basolateral amygdala (BLA), respectively. d No significant difference in mGlu₇ receptor expression of the CeA of the amygdala was found between the two strains. e Representative image of mGlu₇ receptor mRNA staining in the amygdala of B6 mice. f Representative image of mGlu₇ receptor mRNA staining in the amygdala of S1 mice. *Significant using Student’s t test when compared to B6. n = 6

Fig. 2

In situ hybridisation of mGlu₇ receptor in the hippocampus of B6 and S1 mice. a–c Densitometric analysis showing the S1 mice had increased levels of mGlu₇ receptor in the hippocampus (CA1 + CA3), CA1 and CA3 regions of the hippocampus. d No significant difference in mGlu₇ receptor expression of the dentate gyrus of the hippocampus was found between the two strains. e Representative image of mGlu₇ receptor mRNA staining in the hippocampus of B6 mice. f Representative image of mGlu₇ receptor mRNA staining in the hippocampus of S1 mice. *Significant using Student’s t test when compared to B6. n = 6

Fig. 3

In situ hybridisation of mGlu7 receptor in the prefrontal cortex of B6 and S1 mice. a–c No significant difference in mGlu7 receptor expression in the prefrontal cortex was found between the two strains. d Representative image of mGlu7 receptor mRNA staining in the prefrontal cortex of B6 mice. e Representative image of mGlu7 receptor mRNA staining in the prefrontal cortex of S1 mice. CgL = cingulate gyrus, PrL = prelimbic region, IL = infralimbic. n = 6