Abstract
Increasing evidence implicates the microbiota in the regulation of brain and behaviour. Germ‐free mice (GF; microbiota deficient from birth) exhibit altered stress hormone signalling and anxiety‐like behaviours as well as deficits in social cognition. Although the mechanisms underlying the ability of the gut microbiota to influence stress responsivity and behaviour remain unknown, many lines of evidence point to the amygdala and hippocampus as likely targets. Thus, the aim of this study was to determine if the volume and dendritic morphology of the amygdala and hippocampus differ in GF versus conventionally colonized (CC) mice. Volumetric estimates revealed significant amygdalar and hippocampal expansion in GF compared to CC mice. We also studied the effect of GF status on the level of single neurons in the basolateral amygdala (BLA) and ventral hippocampus. In the BLA, the aspiny interneurons and pyramidal neurons of GF mice exhibited dendritic hypertrophy. The BLA pyramidal neurons of GF mice had more thin, stubby and mushroom spines. In contrast, the ventral hippocampal pyramidal neurons of GF mice were shorter, less branched and had less stubby and mushroom spines. When compared to controls, dentate granule cells of GF mice were less branched but did not differ in spine density. These findings suggest that the microbiota is required for the normal gross morphology and ultrastructure of the amygdala and hippocampus and that this neural remodelling may contribute to the maladaptive stress responsivity and behavioural profile observed in GF mice.
Highlights
A rapidly growing body of evidence points to a role of the microbiota in the regulation of brain and behaviour
Data were obtained from mice with at least one intact and undamaged amygdala or hippocampus (CC: n = 5–6; Germ-free mice (GF): n = 5–8)
There were no significant hemispheric differences in amygdalar or hippocampal volume in either conventionally colonized (CC) or GF mice (P > 0.05 for all regions), hemisphere means were used for these analyses
Summary
A rapidly growing body of evidence points to a role of the microbiota in the regulation of brain and behaviour. The gut microbiota is required for development of the hypothalamic–pituitary–adrenal (HPA) axis, optimal stress responsivity and social cognition (Neufeld et al, 2011; Clarke et al, 2013; Desbonnet et al, 2014). We and others have previously shown that GF mice exhibit exaggerated HPA axis responses to acute stressors, reduced anxiety-like behaviours and deficits in social cognition (Sudo et al, 2004; Heijtz et al, 2011; Neufeld et al, 2011; Clarke et al, 2013; Desbonnet et al, 2014; Arentsen et al, 2015), effects which are influenced by the amygdala and hippocampus (Sah et al, 2003; Ledoux, 2007; Tovote et al, 2015). Signalling between the basolateral amygdala (BLA) and the ventral hippocampus modulates both anxiety and social behaviours (Felix-Ortiz et al, 2013; Allsop et al, 2014; Felix-Ortiz & Tye, 2014)
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