MODULATING THE MODULATORS: CHEMOGENETIC DISSECTION OF BULBAR DOPAMINERGIC CONTRIBUTIONS TO OLFACTORY BEHAVIOUR

Dopaminergic neurons constitute a distinct class of interneurons in the olfactory bulb (OB), most of which retain lifelong regenerative capacity. Although dopamine modulates olfactory-related behaviours, the specific contribution of OB dopaminergic neurons to odour detection and discrimination remains unclear. Previous studies often lack anatomical specificity, are confounded by midbrain dopaminergic activity, and use diverse behavioural paradigms, resulting in inconsistent conclusions. Here, we used immunohistochemistry to confirm that the number of tyrosine hydroxylase (TH)-expressing neurons in the OB remains stable across life stages. To investigate the causal role of this stable but non-dominant dopaminergic population, we stereotaxically injected inhibitory or excitatory DREADD viruses into the OB of adult dopamine transporter (DAT)-Cre mice, selectively targeting bulbar DA neurons. After one month of DREADD expression, clozapine-N-oxide (CNO) was administered intraperitoneally to transiently inhibit or activate these neurons, and mice were assessed in a battery of olfactory tasks, including odour habituation, sensitivity and discrimination tests, as well as responses to appetitive and aversive stimuli. Odours were delivered using a custom olfactometer and behaviour was quantified to measure time spent near the odour port and locomotion, while side-view videos were analysed with DeepLabCut to assess sniffing and rearing. Silencing OB DA neurons altered different aspects of behaviour, particularly reducing attraction to appetitive odours, and increased sensitivity to specific odours, enabling detection at lower concentrations. These findings highlight a specific role for OB dopaminergic interneurons in odour-guided behaviour.