Ruxanda C, Alzheimer C, Zheng F (2025)
Publication Language: English
Publication Type: Journal article
Publication year: 2025
Book Volume: 26
Article Number: 7172
Journal Issue: 15
DOI: 10.3390/ijms26157172
B-raf (rapidly accelerated fibrosarcoma) is a crucial player within the ERK/MAPK signaling pathway. In the CNS, B-raf has been implicated in neuronal differentiation, long-term memory, and major depression. Mice with forebrain neuron-specific B-raf knockout show behavioral deficits in spatial learning tasks and impaired hippocampal long-term potentiation (LTP). To elucidate the mechanism(s) underlying diminished synaptic plasticity in B-raf-deficient mice, we performed whole-cell recordings from CA1 pyramidal cells in hippocampal slices of control and B-raf mutant mice. We found that the NMDA/AMPA ratio of excitatory postsynaptic currents (EPSCs) at the Schaffer collateral—CA1 pyramidal cell synapses was significantly reduced in B-raf mutants, which would at least partially account for their impaired LTP. Interestingly, the reduced NMDA component of field postsynaptic potentials in mutant preparations was partially reinstated by blocking the apamin-sensitive small-conductance Ca2+-activated K+ (SK) channels, which have also been reported to modulate hippocampal LTP and learning tasks. To determine the impact of B-raf-dependent signaling on SK current, we isolated the apamin-sensitive tail current after a strong depolarizing event and found indeed a significantly bigger SK current in B-raf-deficient cells compared to controls, which is consistent with the reduced action potential firing and the stronger facilitating effect of apamin on CA1 somatic excitability in B-raf-mutant hippocampus. Our data suggest that B-raf signaling readjusts the delicate balance between NMDA receptors and SK channels to promote synaptic plasticity and facilitate hippocampal learning and memory.
APA:
Ruxanda, C., Alzheimer, C., & Zheng, F. (2025). Forebrain-Specific B-raf Deficiency Reduces NMDA Current and Enhances Small-Conductance Ca2+-Activated K+ (SK) Current. International Journal of Molecular Sciences, 26(15). https://doi.org/10.3390/ijms26157172
MLA:
Ruxanda, Cornelia, Christian Alzheimer, and Fang Zheng. "Forebrain-Specific B-raf Deficiency Reduces NMDA Current and Enhances Small-Conductance Ca2+-Activated K+ (SK) Current." International Journal of Molecular Sciences 26.15 (2025).
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