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gage neurogenesis

gage neurogenesis - Psychology and Aging 2008 Vol 23 No 4...

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Stem-Cell-Associated Structural and Functional Plasticity in the Aging Hippocampus Sebastian Jessberger ETH Zu ¨rich Fred H. Gage Salk Institute for Biological Studies Aging frequently leads to a functional decline across multiple cognitive domains, often resulting in a severe reduction in life quality and also causing substantial care-related costs. Understanding age- associated structural and functional changes of neural circuitries within the brain is required to improve successful aging. In this review, the authors focus on age-dependent alterations of the hippocampus and the decline of hippocampal function, which are critically involved in processes underlying certain forms of learning and memory. Despite the dramatic reductions in hippocampus-dependent function that accompany advancing age, there is also striking evidence that even the aged brain retains a high level of plasticity. Thus, one promising avenue to reach the goal of successful aging might be to boost and recruit this plasticity, which is the interplay between neural structure, function, and experience, to prevent age-related cognitive decline and age-associated comorbidities. Keywords: adult neurogenesis, aging, plasticity, hippocampus, learning and memory The mammalian brain is challenged throughout life with novel experiences that shape behavior, personality, and cognitive abili- ties. Thus, the brain has to be able to integrate novelty into the neural circuitries that were formed on the basis of earlier experi- ences. The dynamic but constant adaptation of the brain to external stimulation, which seems to be a pivotal component of the central nervous system to fulfill its manifold tasks, is thought to be based on structural changes within neural networks that are induced by what we, as humans, see, hear, feel, dream, taste, think, or, in more general terms, experience. For a long time it was thought that the complex architecture and the relative stability of certain memories strongly argued against a constant remodeling of neural circuitries. However, modern molecular and electrophysiological techniques, as well as in vivo imaging tools, have provided strong support for the concept of a constantly adapting central nervous system (Bliss & Collingridge, 1993; Cole, Saffen, Baraban, & Worley, 1989; Lendvai, Stern, Chen, & Svoboda, 2000; Toni, Buchs, Nikonenko, Bron, & Muller, 1999). The interaction between the brain and the environment has generated the concept of plasticity . There is no strict definition of the term, but plasticity is mostly used to de- scribe the effects of experience on the structure, connectivity, and functional behavior of either single cells or neural ensembles. The classic example of plasticity within the adult brain is long-term potentiation (LTP): High-frequency stimulation leads to long- lasting changes in synaptic potentiation, resulting in structural and functional modifications of connected neurons (Bliss & Col- lingridge, 1993). Even though direct proof is still missing, a current hypothesis is that LTP might be the cellular correlate of
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