A role for adult TLX-positive neural stem cells in learning and behaviour

Chun Li Zhang, Yuhua Zou, Weimin He, Fred H. Gage, Ronald M. Evans

Research output: Contribution to journalArticle

398 Scopus citations

Abstract

Neurogenesis persists in the adult brain and can be regulated by a plethora of external stimuli, such as learning, memory, exercise, environment and stress. Although newly generated neurons are able to migrate and preferentially incorporate into the neural network, how these cells are molecularly regulated and whether they are required for any normal brain function are unresolved questions. The adult neural stem cell pool is composed of orphan nuclear receptor TLX-positive cells. Here, using genetic approaches in mice, we demonstrate that TLX (also called NR2E1) regulates adult neural stem cell proliferation in a cell-autonomous manner by controlling a defined genetic network implicated in cell proliferation and growth. Consequently, specific removal of TLX from the adult mouse brain through inducible recombination results in a significant reduction of stem cell proliferation and a marked decrement in spatial learning. In contrast, the resulting suppression of adult neurogenesis does not affect contextual fear conditioning, locomotion or diurnal rhythmic activities, indicating a more selective contribution of newly generated neurons to specific cognitive functions.

Original languageEnglish (US)
Pages (from-to)1004-1007
Number of pages4
JournalNature
Volume451
Issue number7181
DOIs
StatePublished - Feb 21 2008

ASJC Scopus subject areas

  • General

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