Peptidergic Neuromodulation of Sensory Representation in the Brain

ended

Animals interact with and respond to their environment by processing sensory inputs such as visual and auditory cues, touch, taste and smell. How an animal responds to sensory inputs however depends on its internal state (e.g. sleep, wakefulness, stress, fed or starved conditions), such that the same sensory input can produce different behaviours. Neuromodulators play an important role in mediating the internal state of the animal. Neuropeptide Y (NPY) and Gonadotropin-releasing hormone (GnRH) are neuropeptides that are conserved across vertebrates and modulate feeding and reproductive behaviours, antagonistically. They are produced by discrete neuronal populations, and are dispersed widely throughout the brain. Studies suggest that both GnRH/NPY modulate the basal olfactory response by altering the synaptic properties of olfactory receptor neurons. However, it is not known how GnRH/NPY influence the processing of chemosensory information in the olfactory bulb (OB) and ultimately odour driven behaviour. Here, I will use an optically transparent and genetically amenable vertebrate model, zebrafish to study brain function and behaviour. First, I will use genetic methods to specifically label, and visualise the activity of the GnRH/NPY neurons in response to natural odours ex vivo. Next, I will manipulate the activity of these neurons using optogenetics and by expressing neurotoxin/cell ablation genes, and study the effect on olfactory processing in the OB. Finally, after manipulating the activity of GnRH/NPY neurons, I will analyse the effect on odour driven behaviour. This will reveal the role of these neuromodulators in olfactory processing and hence on odour driven behaviour in vertebrates. This project unites my expertise in molecular genetics with that of my host in frontier neuroscience to address a fundamental question of sensory processing, relevant for understanding disorders in which behaviour is decoupled from internal state (e.g. obesity/anorexia).