Genetics of A. californica

o       Representative of mollusks, the 2nd largest phylum

o       How gene expression in different cells affect neural function and behavior.

The aplysia genome is being sequenced because it is representative of the mollusks, the second-largest animal phylum. Despite its size, it is not well understood genomically. Much stands to be gained because the mollusk phylum has a long paleological record (due to the shells many mollusks carry)(1).

Aplysia is controlled by similar homeobox genes as other species. It’s transcriptome in particular is often studied to look for growth factors and receptors that influence neural development, as well as genes involved in synapse formation, memory, and behavior(2). Aplysia was chosen as a model organism in part because its neurons are large enough to generate sufficient mRNA to make a cDNA library. During short-term memory formation, there is no change in transcription or translation levels of the neurons. However, long-term memory requires synthesis of new proteins.

CREB-1a (cAMP response element binging protein) binds target genes whose promoters contain a CRE (cAMP-response element) sequence. Among the immediately upregulated genes are CAAT box enhancer binding protein and activation factor, which together activate more genes that strengthen the conditioned synapse.

Figure 1

Figure 1

Memory suppressor genes such as ApCREB-2 which represses transcription of ApCREB-1a help regulate the formation of long-term memories and ensure that only relevant things are stored long-term.

Despite nuclear activation of genes which could strengthen all synaptical connections formed by the neuron, only the conditioned synapses are strengthened by the cell. This is in part due to localized transcription of mRNAs. The synapses are marked by the original signal, which in initial experiments was a puff of serotonin. This demonstrated a new function of neurotransmitters.

These results have been shown to be applicable to more complex memory formation in the mouse hippocampus. During late-phase long-term potentiation of the mouse hippocampus, PKA mediates gene activity through a MAPK and CREB to create new synaptic connections. This activity is opposed by calcineurin, a phosphatase which negatively regulates the same proteins as PKA(3). Aplysia’s genetic mechanisms are a reasonable model for the mechanisms of memory formation. However, questions still remain about the recall of explicit memories and how this information could be applied to humans experiencing memory formation malfunctions.

Resources

Broad Institute

Aplysia Genome Project page

Genome Resources for Molluscan Neurobiologists

Links to the NCBI database and updates on the progress of                                                                                                              sequencing ( updated March 4, 2011).

1.         Heyland, A., Vue, Z., Voolstra, C. R., Medina, M., and Moroz, L. L. (2011) Developmental transcriptome of Aplysia californica’, Journal of Experimental Zoology Part B: Molecular and Developmental Evolution 316B, 113-134.

2.         Croll, R. P. (2009) Developing Nervous Systems in Molluscs: Navigating the Twists and Turns of a Complex Life Cycle, Brain, Behavior & Evolution 74, 164-176.

3.         Kandel, E. R. (2001) The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses, Science 294, 1030-1038.

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