Molecular and cellular mechanisms of oestrus state-dependent odour valence Modulation

This project addresses long-standing questions in sensory neurobiology that have been extraordinarily difficult to address using traditional methods - how natural odour valence is encoded and modulated. The olfactory system translates the detection of volatile chemicals (odours) into perceptual features such as odour identity, intensity and valence to generate appropriate behavioural responses. Odour valence is a particularly critical feature as it elicits appropriate aversion and attraction – motivated behaviours that are crucial for survival. In humans, odour valence is the most salient feature of odours, plays an important role in food choice and social interactions, and is altered in several neurodegenerative diseases as well as during aging. Despite its importance, the mechanisms underlying valence coding remain largely elusive. Importantly, odour valence can be significantly modulated by several factors including internal state (e.g., hormonal status, metabolism), context and experience making it difficult to determine where in the brain, and how, encoding and modulation of odour valence takes place.
Thus, to identify the neural basis of valence coding, it is crucial to causally link changes in neuronal activity with changes in valence-driven behaviour by manipulating the specific receptor inputs – a major aim of this proposal.
Most studies artificially impose changes in valence on odours using aversive/appetitive conditioning due to the lack of a model system in which innate valence can be manipulated. However, it is unknown if conditioned and innate valence are encoded in the same way. My preliminary work has identified a new model system in which non-conditioned valence of a volatile social odour is naturally modulated by neuroendocrine state in the mouse. Here, I propose to exploit this model to dissect the cellular and circuit mechanisms that underlie naturally occurring odour valence modulation using a combination of advanced mouse genetics, simultaneous physiological recordings and behaviour as well as viral tracing. This work addresses the fundamental question of how sensory inputs are integrated with internal state to generate appropriate behavioural output.