Enhancement of long-term memory retention and short-term synaptic plasticity in cbl-b null mice.
The cbl-b gene is a member of the cbl protooncogene family. It encodes a protein with multiple domains, which can interact with other proteins in a variety of signaling pathways. The functions of cbl family genes in the brain are unknown. In this report, we used genetic, immunohistochemical, behavioral, and electrophysiological approaches to study the role of cbl-b in learning and memory. Cbl-b null mice developed normally and had no abnormalities in their locomotor performance. In spatial learning and memory studies, cbl-b null and WT mice performed similarly during training. To test memory retention, two probe trials were used. cbl-b null mice performed slightly better 1 day after training. However, in the probe trial 45 days after training, the cbl-b null group showed significantly higher memory retention than WT mice, suggesting an enhancement of long-term memory. Using electrophysiological approaches, we found there was enhanced paired-pulse facilitation in the Schaffer Collateral-CA1 glutamatergic synapses of the cbl-b null mice. On the other hand, there was no difference in long-term potentiation between the two groups of mice. In summary, we provide evidence that (i) cbl-b protein is concentrated in the synaptic regions of CA1, CA3, and the dentate gyrus of the hippocampus; (ii) cbl-b null mice have enhanced long-term memory; and (iii) cbl-b null mice show an enhancement in short-term plasticity. These results indicate that cbl-b is a negative regulator of long-term memory, and its neuronal mechanism regulates synaptic transmission in the hippocampus.
Tan
Dong Ping
DP
Blanchette Rockefeller Neurosciences Institute, Rockville, MD 20850, USA. dptan@brni-jhu.org
Liu
Qi-Ying
QY
Koshiya
Naohiro
N
Gu
Hua
H
Alkon
Daniel
D
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009154:Mutation / Q000235:genetics; D009473:Neuronal Plasticity / Q000502:physiology*; D050721:Proto-Oncogene Proteins c-cbl / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D013997:Time Factors
D048868:Adaptor Proteins, Signal Transducing; C118387:Cblb protein, mouse; D050721:Proto-Oncogene Proteins c-cbl