ADULT NEUROGENESIS: INTEGRATION OF NEW NEURONS IN THE PREEXISTING HIPPOCAMPAL NETWORK

SCHINDER AF

Los Cardales, Buenos Aires

Simposio; Exciting Biologies: Biology in Balance; 2009

Cell Press, Foundation Ipsen and Massachussetts General Hospital

The adult dentate gyrus continuously generates a substantial amount of neurons that contribute significantly to hippocampal function. How newly generated neurons integrate in a fully established network in a manner that is both safe and functionally relevant remains a puzzle. Over the last few years we have investigated this phenomenon in detail and found that functional integration is a slow and tightly controlled process: new neurons develop over several weeks and follow a sequence of maturation and connectivity that recapitulates those events occurring during perinatal development. Developing neurons go over a period of enhanced excitability that allows them to maintain a high level of activation even when afferent excitation is weak. This high excitability is transient and decreases to a lower level as neurons approach maturity. When fully mature, new neurons display input and output properties that cannot be distinguished from those of dentate granule cells generated in the developing brain. What are the intrinsic and extrinsic cues that determine the identity and strength of inputs and outputs, the “rules of connectivity”? We hypothesize that a cell-autonomous program determines the amount of excitation and inhibition that a dentate granule cell must gather in order to achieve a target level of intrinsic firing activity. We are currently using retroviral vectors to express a variety of transgenes in dividing progenitor cells of the adult dentate gyrus to investigate how maturation and functional integration are affected when the excitation/inhibition balance is shifted.