Olfaction plays a fundamental role in rodent social recognition and behaviour. Here we demonstrate that associative learning via modulation of olfactory memory results in a conditioned stress response in the absence of the aversive stimulus. Rats were subjected to a single 15 minute daily exposure to a neutral odour (lemongrass oil) over 4 days, either in their home cage (n=8; control) or within a restraint tube (n=8). On day 5 all rats were exposed to the olfactory stimulus for 15 minutes in their home cages. Rats were sacrificed 90 minutes after the odour exposure and brains processed for free-floating immunohistochemistry for Fos and also double labelled for vasopressin (AVP) and corticotrophin releasing factor (CRF). Rats conditioned to the odour with restraint stress showed significantly higher Fos immunoreactivity in AVP neurones in the parvocellular paraventricular nucleus (pPVN, P=0.006) and in CRF positive neurones in the pPVN (P<0.001) and medial amygdala (MeAmy, P=0.005) following odour stimulus alone compared to control rats. Fos immunoreactivity was also significantly elevated in the supraoptic nucleus, MeAmy, magnocellular PVN, pPVN and olfactory bulb (P≤0.05). These data demonstrate that odour conditioning to a stressor elicits activation of both the HPA axis and the olfactory system when exposed to the odour alone. The pairing of a conditioning neutral environmental cue with an aversive stimulus is not a novel concept. However, the use of an olfactory cue to induce a stress response allows us to investigate how olfactory memory during stress exposure is formed. Gaining an understanding of the neuronal basis of learned fear and modulation of specific pathways to attenuate stress associated learning may provide a useful tool in the prevention of fear conditioning to aversive stimuli and be of particular importance in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.
Research supported by the BBSRC.