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Mechanisms of integration of newly generated neurons inthe adult forebrain


The proposal seeks to identify the mechanisms by which newly generated neurons in the adult olfactory bulb (OB) are integrated into a functional sensory processing network. The OB is one of only two brain regions in which newly generated cells continue to replace components of existing circuitry in adult life. How these newborn neurons are integrated into the OB network, establishing functional connections with existing cells and ensuring a seamless turnover of olfactory processing machinery, is an important issue for understanding how sensory information is processed in such a dynamic system. It also has relevance to clinical attempts at stimulating functional endogenous regeneration in the adult brain. Of particular interest is the fact that many newborn OB neurons die after reaching the bulb.

Do these neurons establish initial contacts with existing OB circuitry? If so, does the information received by a newborn OB cell from the existing OB network determine whether or not it survives? We will address the se questions through in vitro electrophysiological recordings of newborn neurons in the adult OB. These recordings will be undertaken both in normal mice and in mice in which electrical activity in the OB has been systematically altered.

We aim to discover whether surviving cells receive particular patterns of input that cells destined to die do not, and whether the survival of newborn OB neurons is affected if those patterns are disrupted. To this end, Matthew Grubb, a British researcher with doctoral experience in in-vivo electrophysiology and developmental neuroscience, will join the Lledo laboratory at the Institut Pasteur in Paris, a world leader in the field of adult neurogenesis and OB function.

The proposal will allow Mr Grubb to diversify his scientific expertise en route to an independent career in neuroscience research, and should generate significant data in an exciting scientific field with important potential clinical applications.

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