14-3-3 proteins are required for hippocampal long-term potentiation and associative learning and memory.
14-3-3 is a family of regulatory proteins highly expressed in the brain. Previous invertebrate studies have demonstrated the importance of 14-3-3 in the regulation of synaptic functions and learning and memory. However, the in vivo role of 14-3-3 in these processes has not been determined using mammalian animal models. Here, we report the behavioral and electrophysiological characterization of a new animal model of 14-3-3 proteins. These transgenic mice, considered to be a 14-3-3 functional knock-out, express a known 14-3-3 inhibitor in various brain regions of different founder lines. We identify a founder-specific impairment in hippocampal-dependent learning and memory tasks, as well as a correlated suppression in long-term synaptic plasticity of the hippocampal synapses. Moreover, hippocampal synaptic NMDA receptor levels are selectively reduced in the transgenic founder line that exhibits both behavioral and synaptic plasticity deficits. Collectively, our findings provide evidence that 14-3-3 is a positive regulator of associative learning and memory at both the behavioral and cellular level.
Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida 32306, and China Academy of Chinese Medical Sciences Institute of Acupuncture and Moxibustion, Beijing 100700, China.
Haifa
H
Qiao
Molly
M
Foote
Kourtney
K
Graham
Yuying
Y
Wu
Yi
Y
Zhou
D048948:14-3-3 Proteins / Q000172:deficiency / Q000502:physiology*; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001362:Avoidance Learning / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003213:Conditioning, Psychological / Q000502:physiology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques
D048948:14-3-3 Proteins; D001426:Bacterial Proteins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria
14-3-3 proteins; NMDA receptors; fear conditioning; long-term potentiation; passive avoidance