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Chunk #17 — Results — LTP fails to stabilize in slices from BAF53b mutant mice

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The neuron-specific chromatin regulatory subunit BAF53b is necessary for synaptic plasticity and memory.
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The Baf53b+/− het mice show robust failure in the expression of LTP. Thus, we wanted to determine if the mice showed deficits in activity induced actin signaling. TBS stimulation activates actin regulatory pathways and alters synapse morphology within the same dendritic spines as shown by a TBS induced increase in spines containing phosphorylated p21-activated kinase (PAK) or its downstream target Cofilin23. Using wide field deconvolution microscopy and immunofluorescent labeling we found that phosphorylated (p) Cofilin has punctate labeling within stratum radiatum of CA1 and colocalizes with PSD95, a marker for excitatory synapses (Fig 6A). Quantification revealed that the intensity profiles of pCofilin puncta colocalized with PSD95 are right shifted in the Baf53b+/− het mice, indicating an increase in more intensely labeled puncta (Fig 6B & 6C). pCofilin has been shown to peak seven min post-TBS24. Therefore, we examined pCofilin at this timepoint in Baf53b+/− het mice and wildtype littermates. Wildtype mice showed a clear, TBS induced increase in the number of densely labeled pCofilin puncta co-localized to PSD95 seven minutes following TBS, while the Baf53b+/− het mice did not show