Neuron-specific regulation of associative learning and memory by MAGI-1 in C. elegans.
BACKGROUND
Identifying the molecular mechanisms and neural circuits that control learning and memory are major challenges in neuroscience. Mammalian MAGI/S-SCAM is a multi-PDZ domain synaptic scaffolding protein that interacts with a number of postsynaptic signaling proteins and is thereby thought to regulate synaptic plasticity [1], [2], [3].


RESULTS
While investigating the behavioral defects of C. elegans nematodes carrying a mutation in the single MAGI ortholog magi-1, we have identified specific neurons that require MAGI-1 function for different aspects of associative learning and memory. Various sensory stimuli and a food deprivation signal are associated in RIA interneurons during learning, while additional expression of MAGI-1 in glutamatergic AVA, AVD and possibly AVE interneurons is required for efficient memory consolidation, i.e. the ability to retain the conditioned changes in behavior over time. During associative learning, MAGI-1 in RIA neurons controls in a cell non-autonomous fashion the dynamic remodeling of AVA, AVD and AVE synapses containing the ionotropic glutamate receptor (iGluR) GLR-1 [4]. During memory consolidation, however, MAGI-1 controls GLR-1 clustering in AVA and AVD interneurons cell-autonomously and depends on the ability to interact with the beta-catenin HMP-2.


CONCLUSIONS
Together, these results indicate that different aspects of associative learning and memory in C. elegans are likely carried out by distinct subsets of interneurons. The synaptic scaffolding protein MAGI-1 plays a critical role in these processes in part by regulating the clustering of iGluRs at synapses.
Stetak
Attila
A
Institute of Zoology, University of Zürich, Zürich, Switzerland. a.stetak@unibas.ch
Hörndli
Frederic
F
Maricq
Andres V
AV
van den Heuvel
Sander
S
Hajnal
Alex
A
D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051528:Guanylate Kinases / Q000235:genetics* / Q000502:physiology*; D007858:Learning; D008568:Memory; D008954:Models, Biological; D008957:Models, Genetic; D009068:Movement; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D013569:Synapses
D029742:Caenorhabditis elegans Proteins; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases; C540161:MAGI-1 protein, C elegans