In the adult brain, the dorsal and ventral hippocampus has been implicated in learning/memory and affective behaviors, respectively, whereas the olfactory bulb is involved in olfaction. Immediately after the initial discovery of neurogenesis in the postnatal rat hippocampus, Altman suggested that new neurons are critical for learning and memory (Altman, 1967). While still under intensive debate, analyses at the cellular, circuitry, system, and behavioral

levels over the past few years have generated mounting evidence supporting critical contributions PD 332991 of adult-born neurons to hippocampal and olfactory bulb functions (reviewed by Deng et al., 2010 and Lazarini and Lledo, 2011; see also Aimone et al., 2011 and Sahay et al., 2011 in this issue). At the cellular level, newborn neurons display special properties that are distinct from mature counterparts. Synaptically connected newborn neurons exhibit hyperexcitability PD0332991 cell line and enhanced synaptic plasticity of their glutamatergic inputs during a critical period of maturation in both hippocampus and olfactory bulb (Figure 2 and Figure 3), which may allow newly integrated adult-born neurons to make unique contribution to information processing. At the circuitry level, adult-born neurons are responsible for certain special properties

of the local circuitry. Slice electrophysiology has shown that long-term potentiation (LTP) of evoked field potentials induced by tetanic stimulation of the afferent medial perforant pathway is abolished by radiation to abrogate adult neurogenesis (Snyder et al., 2001). One potential mechanism is a much-reduced sensitivity of newborn neurons to powerful perisomatic GABAergic inhibition from basket interneurons during the critical period (Ge et al., 2008). In vivo recording from the dentate gyrus in anesthetized mice has shown that elimination of adult neurogenesis leads to decreased amplitude in perforant-path evoked responses Phosphatidylinositol diacylglycerol-lyase and a marked increase in both the amplitude

of spontaneous γ-frequency bursts in the dentate gyrus and the synchronization of dentate neuron firing to these bursts (Lacefield et al., 2010). At the system level, a number of computational models of adult neurogenesis have provided clues on how the addition of new neurons may alter neural network properties and have suggested distinct roles for adult-born neurons at different stages of neuronal maturation (reviewed by Aimone and Gage, 2011). More importantly, these computational approaches can guide future experiments to specifically test new predictions. At the behavioral level, the field has gone through the initial stage of correlative studies with manipulations that lack specificity and general behavioral tests, to a stage combining more targeted behavioral tests and sophisticated genetic approaches with enhanced temporal and spatial specificity.