Neuroligin-3-Mediated Synapse Formation Strengthens Interactions between Hippocampus and Barrel Cortex in Associative Memory.

Memory traces are believed to be broadly allocated in cerebral cortices and the hippocampus. Mutual synapse innervations among these brain areas are presumably formed in associative memory. In the present study, we have used neuronal tracing by pAAV-carried fluorescent proteins and neuroligin-3 mRNA knockdown by shRNAs to examine the role of neuroligin-3-mediated synapse formation in the interconnection between primary associative memory cells in the sensory cortices and secondary associative memory cells in the hippocampus during the acquisition and memory of associated signals. Our studies show that mutual synapse innervations between the barrel cortex and the hippocampal CA3 region emerge and are upregulated after the memories of associated whisker and odor signals come into view. These synapse interconnections are downregulated by a knockdown of neuroligin-3-mediated synapse linkages. New synapse interconnections and the strengthening of these interconnections appear to endorse the belief in an interaction between the hippocampus and sensory cortices for memory consolidation.

Overexpression of protocadherin 7 inhibits neuronal survival by downregulating BIRC5 in vitro.

Protocadherins (Pcdhs) are widely-expressed transmembrane proteins in the nervous system. Recent studies suggest that Pcdhs play multiple critical roles during neuronal development. However, the cellular mechanisms of Pcdh7 in neurons are still largely unknown. In the current study, we demonstrated that the expression of Pcdh7 during mouse brain development was regulated spatiotemporally. We observed that the elevated expression of Pcdh7 led to activation of the intrinsic apoptotic pathway in primary cortical neurons. Whole transcriptome sequencing revealed that 12 genes were involved in the apoptotic pathway including baculoviral inhibitor of apoptosis (IAP) repeat containing 5 (BIRC5). The neuronal apoptosis caused by Pcdh7 overexpression could be significantly inhibited by either a missense mutation in the conserved motif CM2 domain of Pcdh7 or BIRC5 overexpression. These results suggest the existence of Pcdh7-BIRC5 signaling cascade in the cortical neurons and represent a potential therapeutic area for further investigation.