Sussex Neuroscience

Professor George Kemenes

GeorgeEpigenetic mechanisms of long-term memory after single-trial classical conditioning

It is well-known that in association with other stimuli, a single but highly salient event can trigger long-term memory (LTM). It is not known however, how a single episode of learning can have immediate access to the complex molecular processing machinery that has been found to be involved in the formation of LTM during prolonged learning in all animal models of learning and memory. Addressing this key question at a fundamental level is the major objective of current research in my laboratory.

We are using an established invertebrate model, Lymnaea stagnalis, to test the hypothesis that epigenetic control mechanisms, specifically, histone modifications and microRNA-mediated regulation of gene function, are critical elements for LTM to form after a single episode of learning. The unique advantage of this system is that it permits a fully integrated analysis of the molecular mechanisms of learning, from the behavioural and systems level down to identified circuits and single neurons.

Several major conserved molecular pathways of LTM (e.g., PKA/MAPK/CREB) with a known ability to interact with epigenetic mechanisms have already been identified in Lymnaea. Together with the detailed knowledge of the ‘learning and memory network' in this species, the understanding of these key molecular pathways will enable us to test their functional relationship with epigenetic control mechanisms underlying LTM. In the PhD project, a combination of behavioural, molecular, electrophysiological and imaging methods will be used to conduct a top-down analysis of the role of epigenetic mechanisms in consolidation and reconsolidation of LTM after single-trial food-reward classical conditioning in Lymnaea. The project would best suit a student with an already existing strong background in molecular level analysis. Training in behavioural methods, electrophysiology and imaging will be provided as part of the project.

Selected publications

(For full list of publications and more details about the lab, please visit: http://www.sussex.ac.uk/lifesci/kemeneslab/)

Naskar S, Wan H, Kemenes G. pT305-CaMKII stabilizes a learning-induced increase in AMPA receptors for ongoing memory consolidation after classical
conditioning. Nat Commun. 2014 5:3967. doi: 10.1038/ncomms4967.

Pirger Z, Naskar S, László Z, Kemenes G, ReglÅ‘di D, Kemenes I. Reversal of Age-Related Learning Deficiency by the Vertebrate PACAP and IGF-1 in a Novel Invertebrate Model of Aging: The Pond Snail (Lymnaea stagnalis). J Gerontol A Biol Sci Med Sci. 2014 69(11):1331-8. doi: 10.1093/gerona/glu068.

Nikitin ES, Balaban PM, Kemenes G. Nonsynaptic plasticity underlies a compartmentalized increase in synaptic efficacy after classical conditioning.
Curr Biol. 2013 23(7):614-9. doi: 10.1016/j.cub.2013.02.048.

Korneev SA, Kemenes I, Bettini NL, Kemenes G, Staras K, Benjamin PR, O'Shea M. Axonal trafficking of an antisense RNA transcribed from a pseudogene is regulated by classical conditioning. Sci Rep. 2013 3:1027. doi: 10.1038/srep01027.