Distinct connectivity of newly-generated dopaminergic neurons in the adult brain?

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A healthy brain requires its constituent cells, or neurons, to be properly connected to each other. These connections can involve thousands of different inputs arriving onto a single cell, before that cell integrates the incoming information and sends an output signal to a range of highly specific downstream partners. In this way, neuronal networks transform input information into a suitably-processed output signal, so that sensory experience, for example, can control our behaviour. Understanding the way in which neurons are connected, then, is crucial in understanding their function. This is particularly true for a unique type of neuron: those born in the adult brain. These cells are in the great minority, because most of our neurons are generated before birth and lack the ability to regenerate after injury or disease. However, in a few specialised zones of the mature mammalian brain, new neurons are continually produced throughout life in a process known as adult neurogenesis. This generates entirely new neurons which must integrate into existing networks, receiving inputs and sending outputs to contribute to circuit function.The goal of our proposal is to study these newly-formed connections made by a particular type of adult-generated neuron. In the olfactory bulb - the first part of the brain to process smell information arriving from the nose - dopaminergic neurons play a key role in modulating sensory signals at their earliest stages, and these cells can be generated throughout life. However, it is entirely unknown whether the input and output connections, and therefore the circuit function of these neurons, is unique to dopaminergic cells produced in adulthood. By using a combination of cutting-edge approaches, we will ask whether adult neurogenesis produces cells with unique connectivity in this sensory-processing circuit.In addressing this important basic biological question, our work has the potential to impact on healthcare in the UK. Our study of the olfactory system may inform future approaches to treat debilitating smell disorders such as anosmia and hyposmia, which have a huge impact on quality of life and affect at least 20% of the population. Our focus on dopaminergic neurons may inform treatments for disorders where these cells are lost in later life, such as Parkinson's Disease. And our study of new neurons in old circuits has the wider promise of informing any attempt to repair brain damage by adding freshly-generated cells to perturbed networks.