FUNCONAOB · Mechanisms of integration of newly generated neurons inthe adult forebrain

Final Activity Report Summary - FUNCONAOB (Mechanisms of integration of newly generated neurons in the adult forebrain)

Until approximately ten years ago we used to think that no new cells, or neurons, were born in the adult brain. Brain damage was therefore thought to be permanent, since damaged tissue could never be replaced by fully-functioning, adult-born cells. Nevertheless, recent work in my host laboratory and elsewhere dispelled this myth. We now know that at least two regions of the mammalian brain produce new neurons throughout adult life. The race is now on to fully understand how this process of adult neurogenesis operates, with the hope that we could reproduce it to repair the brains of people with degenerative disorders or serious head trauma. My project focussed on providing important new information concerning basic processes of adult neurogenesis in the olfactory system. The olfactory bulb, which is the first area of the brain to receive information from the nose, has two populations of neurons which undergo neurogenesis in the adult, namely granule cells and Periglomerular cells (PGCs). Both are born outside the olfactory bulb and must migrate several millimetres before reaching their final destination, which is a process that takes several days. Once in the correct place in the olfactory bulb, these cells start to form connections with the resident population of cells around them and, over a couple of months, they must decide which connections to maintain and which to leave to degenerate. The pattern of connections formed by a newly-born olfactory bulb cell will determine the way it functions in olfactory processing, which in turn will influence how the brain perceives odorants. The decision-making process made by adult-born neurons as they integrate into an already-functioning area of the brain is therefore vital for our sense of smell. I investigated this process by looking at the connections formed between PGCs and the pathway that brings olfactory information from the nose, i.e. the olfactory nerve. This connection, or synapse, is one of the very first in olfactory processing, yet we know nothing regarding how it develops in the young brain, or how it wires up when newborn cells integrate themselves into the adult brain. I used electrophysiological techniques, which involved recording tiny electrical currents in living neurons, to describe the maturation of this connection both in postnatal development and adult neurogenesis. My project provided a good deal of basic, useful information regarding the maturation of this synapse, information that others would hopefully build on in our search to understand adult neurogenesis. However, my most important scientific achievement was to show that this connection matured on one side only. While the 'presynaptic' side of the connection, i.e. the fibres coming from the nose, remained functionally constant at all times, the 'postsynaptic' side of the connection, i.e. the parts of the PGC that received the nose's signal, changed considerably. Moreover, these changes seemed to be very similar regardless if the cell was a PGC in a young developing brain or a newborn PGC in the adult brain which had to integrate into an already functioning olfactory bulb. There were many experiments yet to carry out in order to build on these basic data, but we hoped they would inspire exciting future therapies for adult neurogenesis-based brain repair.

Data: CORDIS, © European Union