Molecular organization of Octopus brains: First insights into unique memory center signaling

Cephalopod molluscs (Octopus, cuttlefish, squid, Nautilus) have independently evolved neural circuitry that controls stereotyped and learned behaviors whose complexity rivals that of many mammals. The Vertical Lobe (VL), a functional analog to the mammalian hippocampus, is unique to cephalopods and mediates spatial memory and visual discrimination. We used RNA-seq/transcriptome profiling, and anatomical validation using in-situ hybridization to identify and map candidate cephalopod memory molecules. We identified 17,841 transcripts in the VL and found 12,379 (69.4%) appear to be cephalopod-specific, while many memory related signal molecules were not identified in the VL transcriptome. These data suggest that cephalopods used a distinct subset of genes and signaling molecules (SM) to form memory circuits. Previously, we identified the neuropeptide complement in the Aplysia genome, and found 22 homologs in Octopus VL. We mapped the expression of 17 of these conserved neuropeptides and two of them, TkP and WhP, localize to the VL circuit. WhP is expressed in the cell bodies of the MSF, where the afferent tract to the VL begins, and TkP localizes to cell bodies of each VL gyrus. Next, we used computational predictions and manual annotation to identify putative SM in the VL. We identified four cephalopod-specific abundant transcripts, one of which (IRP) maps to cell bodies in the VL. Two others are highly expressed in Octopus brain, but absent in the ancestrally branching Nautilus CNS. This expansion of novel SM in the VL circuit is likely a key feature of cephalopod memory systems, implying extensive parallel evolution of cephalopod brains. Supported by NSF, NIH & NASA