To further explore the link between the impairments in maintenance of long-term potentiation and cofilin phosphorylation we examined gene expression for GO terms involved in actin cytoskeleton and the post synaptic density. Most genes examined showed similar expression between the Baf53b+/− het mice and the wildtype littermates. However, there were several key genes that showed misregulation either at baseline (homecage) or following OLM training that are involved in regulating the Rac-PAK and RhoA-LIMK pathways that both culminate in phosphorylation of cofilin and actin cytoskeleton reorganization23 (Supplemental Table S12). For example, mir132 has previously been shown to regulate spine plasticity39,40 and long-term OLM41 by regulating Rac1 activity through translational repression of p250GAP39. Additional regulators of this pathway were also disrupted in the Baf53b+/− het mice including Citron (Rho interacting kinase) and Fhl2 (a member of the four-and-a-half LIM only protein family implicated in linking signaling pathways to transcriptional regulation). Components upstream of the Rac-PAK and RhoA-LIMK were also altered in the Baf53b+/− het mice including the NMDA receptor subunits Grinb2 and Grin2a and Ephrin type-A receptor.
