Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus

Abstract

Neural stem cells in various regions of the vertebrate brain continuously generate neurons throughout life1,2,3,4. In the mammalian hippocampus, a region important for spatial and episodic memory5,6, thousands of new granule cells are produced per day7, with the exact number depending on environmental conditions and physical exercise1,8. The survival of these neurons is improved by learning and conversely learning may be promoted by neurogenesis8,9,10. Although it has been suggested that newly generated neurons may have specific properties to facilitate learning2,10,11, the cellular and synaptic mechanisms of plasticity in these neurons are largely unknown. Here we show that young granule cells in the adult hippocampus differ substantially from mature granule cells in both active and passive membrane properties. In young neurons, T-type Ca2+ channels can generate isolated Ca2+ spikes and boost fast Na+ action potentials, contributing to the induction of synaptic plasticity. Associative long-term potentiation can be induced more easily in young neurons than in mature neurons under identical conditions. Thus, newly generated neurons express unique mechanisms to facilitate synaptic plasticity, which may be important for the formation of new memories.

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Figure 1: Newly generated granule cells in adult hippocampus are defined by high input resistance, PSA-NCAM immunoreactivity and immature dendritic morphology.
Figure 2: Young granule cells have distinct active and passive membrane properties.
Figure 3: T-Type Ca2+ channels lead to enhanced excitability in young granule cells.
Figure 4: Different induction rules for long-term potentiation in young and mature neurons.

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Acknowledgements

We thank M. Frotscher, E. Förster and G. Stuart for critically reading the manuscript, and K. Winterhalter and A. Blomenkamp for technical assistance. Work was supported by the Deutsche Forschungsgemeinschaft.

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Correspondence to Josef Bischofberger.

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Schmidt-Hieber, C., Jonas, P. & Bischofberger, J. Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429, 184–187 (2004). https://doi.org/10.1038/nature02553

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