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Cellular and molecular mechanisms of memory function and dysfunction in a defined invertebrate neuronal network

George Kemenes

Sussex Centre For Neuroscience, University of Sussex, UK

The pond snail Lymnaeastagnalis has provided valuable experimental models for top-down analyses of the cellular and molecular mechanisms of classical conditioning. Recent work in Lymnaea has enabled us to gain new insights into how associative long-term memory (LTM) is formed, expressed and maintained and through this, to understand how a numerically simple nervous system generates complex adaptive behaviours that share characteristics with similar behaviours in mammals . To date, the most detailed information on mechanisms of LTM in Lymnaea has come from experiments using a single-trial food-reward classical conditioning paradigm 1-9. Molecular mechanisms of memory function after single-trial conditioning involve the activation of highly conserved signalling pathways (NO/cGMP/PKG, cAMP/PKA, CaMKII and MAPK), phosphorylation of CREB and de novo RNA and protein synthesis. The role of most of these molecular factors in the consolidation or maintenance of LTM also has been confirmed by molecular (RNAi) or pharmacological blocking experiments, which lead to memory dysfunction 1,3,6,8. A key new finding emerging from our work in Lymnaea is that d epending on how recent or remote consolidated memories are relative to the time of learning, different molecular pathways are activated by memory retrieval and contribute differentially to memory reconsolidation 2. Importantly, a number of novel cellular and molecular processes involved in associative LTM have now been traced from the behavioural level to the level of the well-identified feeding network 3,4 and to single identified neurons 4,5,7. For example, both learning induced non-synaptic plasticity in a key identified modulatory neuron of the feeding network 4,7 and increased transciption of a nitric oxide synthase gene in the same cell 5 have been succesfully linked to behavioural associative memory. Thus our recent work has consolidated Lymnaea as an extremely useful model for learning and memory research using the top-down approach.