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Steel mutant mice are deficient in hippocampal learning but not long-term potentiation
B Motro1, J M Wojtowicz, A Bernstein
1Program in Molecular Biology and Cancer, Samuel Lunenfeld Reseaerch Institute, Mount Sinai Hospital, Toronto, Canada.
Abstract:
Mice carrying mutations in either the dominant white-spotting (W) or Steel (Sl) loci exhibit deficits in melanogenesis, gametogenesis, and hematopoiesis. W encodes the Kit receptor tyrosine kinase, while Sl encodes the Kit ligand, Steel factor, and the receptor-ligand pair are contiguously expressed at anatomical sites expected from the phenotypes of W and Sl mice. The c-kit and Steel genes are also both highly expressed in the adult murine hippocampus: Steel is expressed in dentate gyrus neurons whose mossy fiber axons synapse with the c-kit expressing CA3 pyramidal neurons. We report here that Sl/Sld mutant mice have a specific deficit in spatial learning. These mutant mice are also deficient in baseline synaptic transmission between the dentate gyrus and CA3 but show normal long-term potentiation in this pathway. These observations demonstrate a role for Steel factor/Kit signaling in the adult nervous system and suggest that a severe deficit in hippocampal-dependent learning need not be associated with reduced hippocampal long-term potentiation.
Insights
Steel factor/Kit signaling is crucial for spatial learning in mice. Mutant mice show impaired learning and synaptic transmission in the hippocampus, despite normal long-term potentiation.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Mutations in the dominant white-spotting (W) and Steel (Sl) loci in mice cause deficits in melanogenesis, gametogenesis, and hematopoiesis.
- The W locus encodes the Kit receptor tyrosine kinase, and the Sl locus encodes its ligand, Steel factor.
- Both c-kit and Steel genes are highly expressed in the adult murine hippocampus, suggesting a role in neural function.
Purpose of the Study:
- To investigate the role of Steel factor/Kit signaling in the adult nervous system.
- To determine the effect of Sl mutations on spatial learning and hippocampal function.
Main Methods:
- Utilized Sl/Sld mutant mice, which have a specific deficit in Steel factor.
- Assessed spatial learning abilities in mutant and wild-type mice.
- Examined synaptic transmission and long-term potentiation (LTP) in the hippocampal CA3 pathway.
Main Results:
- Sl/Sld mutant mice exhibited a specific deficit in spatial learning.
- These mice showed deficient baseline synaptic transmission between the dentate gyrus and CA3.
- Long-term potentiation in this hippocampal pathway remained normal in the mutant mice.
Conclusions:
- Steel factor/Kit signaling plays a significant role in the adult nervous system, particularly in hippocampal-dependent spatial learning.
- A severe deficit in learning does not necessarily correlate with reduced hippocampal long-term potentiation.
- This study highlights a novel function for the Steel factor/Kit pathway beyond its known roles in development and hematopoiesis.