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Original Research ARTICLE

Front. Neural Circuits, 27 March 2013 | http://dx.doi.org/10.3389/fncir.2013.00052

CASK and CaMKII function in the mushroom body α′/β′ neurons during Drosophila memory formation

  • School of Physiology and Pharmacology, University of Bristol, Bristol, UK

Ca2+/CaM serine/threonine kinase II (CaMKII) is a central molecule in mechanisms of synaptic plasticity and memory. A vital feature of CaMKII in plasticity is its ability to switch to a calcium (Ca2+) independent constitutively active state after autophosphorylation at threonine 287 (T287). A second pair of sites, T306 T307 in the calmodulin (CaM) binding region once autophosphorylated, prevent subsequent CaM binding and inactivates the kinase during synaptic plasticity and memory. Recently a synaptic molecule called Ca2+/CaM-dependent serine protein kinase (CASK) has been shown to control both sets of CaMKII autophosphorylation events and hence is well poised to be a key regulator of memory. We show deletion of full length CASK or just its CaMK-like and L27 domains disrupts middle-term memory (MTM) and long-term memory (LTM), with CASK function in the α′/β′ subset of mushroom body neurons being required for memory. Likewise directly changing the levels of CaMKII autophosphorylation in these neurons removed MTM and LTM. The requirement of CASK and CaMKII autophosphorylation was not developmental as their manipulation just in the adult α′/β′ neurons was sufficient to remove memory. Overexpression of CASK or CaMKII in the α′/β′ neurons also occluded MTM and LTM. Overexpression of either Drosophila or human CASK in the α′/β′ neurons of the CASK mutant completely rescued memory, confirming that CASK signaling in α′/β′ neurons is necessary and sufficient for Drosophila memory formation and that the neuronal function of CASK is conserved between Drosophila and human. At the cellular level CaMKII overexpression in the α′/β′ neurons increased activity dependent Ca2+ responses while reduction of CaMKII decreased it. Likewise reducing CASK or directly expressing a phosphomimetic CaMKII T287D transgene in the α′/β′ similarly decreased Ca2+ signaling. Our results are consistent with CASK regulating CaMKII autophosphorylation in a pathway required for memory formation that involves activity dependent changes in Ca2+ signaling in the α′/β′ neurons.

Keywords: CASK, CaMKII, memory, Drosophila, mushroom body, calcium imaging, autophosphorylation, disease model

Citation: Malik BR, Gillespie JM and Hodge JJL (2013) CASK and CaMKII function in the mushroom body α′/β′ neurons during Drosophila memory formation. Front. Neural Circuits 7:52. doi: 10.3389/fncir.2013.00052

Received: 11 January 2013; Accepted: 09 March 2013;
Published online: 27 March 2013.

Edited by:

Claude Desplan, NYU, USA

Reviewed by:

Makoto Sato, Kanazawa University, Japan
Gaia Tavosanis, German Center for Neurodegenerative Diseases, Germany

Copyright © 2013 Malik, Gillespie and Hodge. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: James J. L. Hodge, School of Physiology and Pharmacology, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK. e-mail: james.hodge@bristol.ac.uk