The Timing of Differentiation of Adult Hippocampal Neurons Is Crucial for Spatial Memory
By S. Farioli-Vecchioli, D. Saraulli, M. Costanzi, Simone Pacioni, Irene Cinà, M. Aceti, L. Micheli, A. Bacci, Vincenzo Cestari, F. Tirone. 2008
185 citations recorded by the source corpus.
Adult neurogenesis in the dentate gyrus plays a critical role in hippocampus-dependent spatial learning. It remains unknown, however, how new neurons become functionally integrated into spatial circuits and contribute to hippocampus-mediated forms of learning and memory. To investigate these issues, we used a mouse model in which the differentiation of adult-generated dentate gyrus neurons can be anticipated by conditionally expressing the pro-differentiative gene PC3 (Tis21/BTG2) in nestin-positive progenitor cells. In contrast to previous studies that affected the number of newly generated neurons, this strategy selectively changes their timing of differentiation. New, adult-generated dentate gyrus progenitors, in which the PC3 transgene was expressed, showed accelerated differentiation and significantly reduced dendritic arborization and spine density. Functionally, this genetic manipulation specifically affected different hippocampus-dependent learning and memory tasks, including contextual fear conditioning, and selectively reduced synaptic plasticity in the dentate gyrus. Morphological and functional analyses of hippocampal neurons at different stages of differentiation, following transgene activation within defined time-windows, revealed that the new, adult-generated neurons up to 3–4 weeks of age are required not only to acquire new spatial information but also to use previously consolidated memories. Thus, the correct unwinding of these key memory functions, which can be an expression of the ability of adult-generated neurons to link subsequent events in memory circuits, is critically dependent on the correct timing of the initial stages of neuron maturation and connection to existing circuits.
Subfields: Cell Biology, Developmental Neuroscience, Genetics
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Citations in the corpus
- DISC1 regulates neural progenitor proliferation via modulation of GSK3β/β-catenin signaling (2009, background): “Cell 136, 1017–1031, March 20, 2009 ª2009 Elsevier Inc. 1027 spatial memory circuitry (Kee et al., 2007), and a failure of newly born neurons to integrate into previously established circuits results in impaired learning (Farioli-Vecchioli et al., 2008).”
- DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212 (2009, unknown): “The speed of new neuron development during adult neurogenesis also appears to be crucial for spatial memory in rodents (Farioli-Vecchioli et al., 2008).”