Abstract:
Fox urine odour 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) has been known to produce avoidance and freezing – innate defensive behaviours which are believed to be genetically hard-wired. These behaviours indicate a possible stress response due to elevated serum corticosterone. Notably, early life stress (ELS) in humans as well as animal models has been linked to diverse forms of cognitive and sensory deficits in their adult lives. This is because the early postnatal brain continuously experiences developmental processes such as axonal and dendritic growth, and synaptic pruning. Thus, stress experienced during the early-life period can have drastic impacts on the developing brain. Previously, a study from our lab demonstrated that ELS can cause olfactory learning deficits. However, whether the effects of ELS also manifest into innate behaviours remains unanswered. In this thesis, we investigated the effects of early life stress on innate defensiveness in mice. Exposure to TMT resulted in hyperactivity and lesser freezing of ELS mice compared to normally weaned mice of similar age. Further, significantly lesser c-Fos expression in the olfactory bulb (OB) of ELS mice compared to the normally weaned group in response to TMT implies reduced population activity due to chronic stress. Although the circuitry and molecular mechanisms mediating such changes are still under investigation, unpublished data from the lab suggested the role of OB interneurons in predator odour processing and mediating these defensive responses. Our current work further tweaks the activity of these interneurons to discern their plausible role in predator odour processing and innate defensive behaviours in ELS mice using optogenetics. We report increased mobile time in ELS mice while photoactivating the inhibitory network compared to control animals. These results thus confirm the role of OB inhibitory interneurons in modulating threat perception under early life adversity.
