Deficient long-term memory and long-lasting long-term potentiation in mice with a targeted deletion of neurotrophin-4 gene.
We examined the learning and memory of neurotrophin-4 (NT4)-/- mice by using fear conditioning. In both cue and context conditioning, we found significant deficits in the NT4 mutants at 2 and 24 h after training but not at 30 min. Hippocampal slices from the mutant mice showed normal basal synaptic transmission, short-term plasticity, and decremental long-term potentiation (LTP) at the Schaffer collateral-CA1 synapses. These findings, together with the normal short-term memory, suggest that the hippocampal development of NT4-/- mice is largely unaffected. However, consistent with the long-term memory defects, the long-lasting LTP at the same synapses was attenuated significantly in the mutant mice. Our results suggest that NT4 plays a physiological role essential for hippocampus- and amygdala-dependent long-term memory and hippocampal long-lasting LTP and that NT4 may be useful in the therapy of acquired disorders of learning and memory.
Xie
C W
CW
Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, University of California, Los Angeles, CA 90024-1759, USA.
Sayah
D
D
Chen
Q S
QS
Wei
W Z
WZ
Smith
D
D
Liu
X
X
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003213:Conditioning, Psychological; D004594:Electrophysiology; D005239:Fear; D017353:Gene Deletion; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000235:genetics*; D010147:Pain Measurement; D009435:Synaptic Transmission
D009414:Nerve Growth Factors; C073922:neurotrophin 4