Spine formation pattern of adult-born neurons is differentially modulated by the induction timing and location of hippocampal plasticity

PLoS One. 2012;7(9):e45270. doi: 10.1371/journal.pone.0045270. Epub 2012 Sep 14.

Abstract

In the adult hippocampus dentate gyrus (DG), newly born neurons are functionally integrated into existing circuits and play important roles in hippocampus-dependent memory. However, it remains unclear how neural plasticity regulates the integration pattern of new neurons into preexisting circuits. Because dendritic spines are major postsynaptic sites for excitatory inputs, spines of new neurons were visualized by retrovirus-mediated labeling to evaluate integration. Long-term potentiation (LTP) was induced at 12, 16, or 21 days postinfection (dpi), at which time new neurons have no, few, or many spines, respectively. The spine expression patterns were investigated at one or two weeks after LTP induction. Induction at 12 dpi increased later spinogenesis, although the new neurons at 12 dpi didn't respond to the stimulus for LTP induction. Induction at 21 dpi transiently mediated spine enlargement. Surprisingly, LTP induction at 16 dpi reduced the spine density of new neurons. All LTP-mediated changes specifically appeared within the LTP-induced layer. Therefore, neural plasticity differentially regulates the integration of new neurons into the activated circuit, dependent on their developmental stage. Consequently, new neurons at different developmental stages may play distinct roles in processing the acquired information by modulating the connectivity of activated circuits via their integration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Spines / metabolism
  • Dendritic Spines / ultrastructure*
  • Dentate Gyrus / physiology
  • Hippocampus / physiology*
  • Long-Term Potentiation
  • Male
  • Neuronal Plasticity / physiology*
  • Neurons / cytology*
  • Neurons / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • Receptors, N-Methyl-D-Aspartate

Grants and funding

This work was supported by the Core Research for Evolutional Science and Technology (CREST) program of the Japan Science and Technology Agency (JST) to KI, a Grant-in-Aid for Scientific Research to KI, a Grant-in-Aid for Young Scientists B to NO from the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese Government, the Mitsubishi Foundation, the Uehara Memorial Foundation to KI, and the Sasakawa Scientific Research Grant from the Japan Science Society to NO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.