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Rescuing impairment of long-term potentiation in fyn-deficient mice by introducing Fyn transgene
1Laboratory of Neurochemistry, National Institute for Physiological Sciences, Okazaki 444, Japan.
Abstract:
To examine the physiological role of the Fyn tyrosine kinase in neurons, we generated transgenic mice that expressed a fyn cDNA under the control of the calcium/calmodulin-dependent protein kinase IIalpha promoter. With this promoter, we detected only low expression of Fyn in the neonatal brain. In contrast, there was strong expression of the fyn-transgene in neurons of the adult forebrain. To determine whether the impairment of long-term potentiation (LTP) observed in adult fyn-deficient mice was caused directly by the lack of Fyn in adult hippocampal neurons or indirectly by an impairment in neuronal development, we generated fyn-rescue mice by introducing the wild-type fyn-transgene into mice carrying a targeted deletion in the endogenous fyn gene. In fyn-rescue mice, Schaffer collateral LTP was restored, even though the morphological abnormalities characteristic of fyn-deficient mice were still present. These results suggest that Fyn contributes, at least in part, to the molecular mechanisms of LTP induction.
Insights
Fyn tyrosine kinase is crucial for neuronal function, particularly in adult brains. Restoring Fyn in mice with a genetic deletion recovered long-term potentiation (LTP), indicating its direct role in synaptic plasticity.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Fyn tyrosine kinase plays a role in neuronal signaling.
- Fyn-deficient mice exhibit impaired long-term potentiation (LTP).
- The precise role of Fyn in adult neurons and its impact on LTP require further elucidation.
Purpose of the Study:
- To investigate the physiological role of Fyn tyrosine kinase in neurons.
- To determine if Fyn's absence in adult hippocampal neurons directly causes LTP impairment.
- To differentiate between direct effects of Fyn deficiency and developmental deficits on LTP.
Main Methods:
- Generation of transgenic mice expressing a fyn cDNA under the CaMKIIalpha promoter.
- Creation of fyn-rescue mice by introducing a wild-type fyn-transgene into fyn-deficient mice.
- Assessment of Schaffer collateral LTP in fyn-rescue mice and comparison with fyn-deficient and wild-type controls.
Main Results:
- Transgenic Fyn expression was low in neonatal brains but strong in adult forebrain neurons.
- Schaffer collateral LTP was restored in fyn-rescue mice.
- Morphological abnormalities persisted in fyn-rescue mice despite LTP restoration.
Conclusions:
- Fyn tyrosine kinase directly contributes to the molecular mechanisms of LTP induction in adult neurons.
- The findings suggest Fyn's critical role in synaptic plasticity, independent of developmental abnormalities.
- This study clarifies Fyn's physiological significance in mature neuronal function.