Fibroblast growth factor receptor-1 is required for long-term potentiation, memory consolidation, and neurogenesis.
BACKGROUND
Although substantial evidence supports the view that adult neurogenesis is involved in learning and memory, how newly generated neurons contribute to the cognitive process remains unknown. Fibroblast growth factor 2 (FGF-2) is known to stimulate the proliferation of neuronal progenitor cells (NPCs) in adult brain. Using conditional knockout mice that lack brain expression of FGFR1, a major receptor for FGF-2, we have investigated the role of adult neurogenesis in hippocampal synaptic plasticity and learning and memory.


METHODS
The Fgfr1 conditional knockout mice were generated by crossing the Fgfr1-null line, the Fgfr1-flox line, and the Nestin-Cre transgenic mice. Bromodeoxyuridine (BrdU) labeling, slice electrophysiology, and Morris Water Maze experiments were performed with the Fgfr1 conditional mutant mice.


RESULTS
Bromodeoxyuridine labeling experiments demonstrate that FGFR1 is required for the proliferation of NPCs as well as generation of new neurons in the adult dentate gyrus (DG). Moreover, deficits in neurogenesis in Fgfr1 mutant mice are accompanied by a severe impairment of long-term potentiation (LTP) at the medial perforant path (MPP)-granule neuron synapses in the hippocampal dentate. Moreover, the Fgfr1 mutant mice exhibit significant deficits in memory consolidation but not spatial learning.


CONCLUSIONS
Our study suggests a critical role of FGFR1 in adult neurogenesis in vivo, provides a potential link between proliferative neurogenesis and dentate LTP, and raises the possibility that adult neurogenesis might contribute to memory consolidation.
Zhao
Mingrui
M
Section on Neural Development and Plasticity, Laboratory of Cellular & Synaptic Neurophysiology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
Li
Dan
D
Shimazu
Kazuhiro
K
Zhou
Yong-Xing
YX
Lu
Bai
B
Deng
Chu-Xia
CX
D000818:Animals; D001522:Behavior, Animal; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000235:genetics; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D008474:Medial Forebrain Bundle / Q000502:physiology / Q000528:radiation effects; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011930:Reaction Time / Q000502:physiology / Q000528:radiation effects; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000172:deficiency / Q000502:physiology*
D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine