Timed and targeted differential regulation of nitric oxide synthase (NOS) and anti-NOS genes by reward conditioning leading to long-term memory formation.
In a number of neuronal models of learning, signaling by the neurotransmitter nitric oxide (NO), synthesized by the enzyme neuronal NO synthase (nNOS), is essential for the formation of long-term memory (LTM). Using the molluscan model system Lymnaea, we investigate here whether LTM formation is associated with specific changes in the activity of members of the NOS gene family: Lym-nNOS1, Lym-nNOS2, and the antisense RNA-producing pseudogene (anti-NOS). We show that expression of the Lym-nNOS1 gene is transiently upregulated in cerebral ganglia after conditioning. The activation of the gene is precisely timed and occurs at the end of a critical period during which NO is required for memory consolidation. Moreover, we demonstrate that this induction of the Lym-nNOS1 gene is targeted to an identified modulatory neuron called the cerebral giant cell (CGC). This neuron gates the conditioned feeding response and is an essential part of the neural network involved in LTM formation. We also show that the expression of the anti-NOS gene, which functions as a negative regulator of nNOS expression, is downregulated in the CGC by training at 4 h after conditioning, during the critical period of NO requirement. This appears to be the first report of the timed and targeted differential regulation of the activity of a group of related genes involved in the production of a neurotransmitter that is necessary for learning, measured in an identified neuron of known function. We also provide the first example of the behavioral regulation of a pseudogene.
Korneev
Sergei A
SA
Sussex Centre for Neuroscience, School of Life Sciences, University of Sussex, Brighton BN1 9QG, United Kingdom. S.Korneev@sussex.ac.uk
Straub
Volko
V
Kemenes
Ildikó
I
Korneeva
Elena I
EI
Ott
Swidbert R
SR
Benjamin
Paul R
PR
O'Shea
Michael
M
D000818:Animals; D001245:Association Learning / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology; D017952:Ganglia, Invertebrate / Q000201:enzymology / Q000502:physiology*; D005786:Gene Expression Regulation; D008195:Lymnaea / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009474:Neurons / Q000201:enzymology / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics*; D052248:Nitric Oxide Synthase Type I; D000439:Pentanols / Q000494:pharmacology; D011544:Pseudogenes / Q000235:genetics*; D016372:RNA, Antisense / Q000096:biosynthesis / Q000235:genetics*; D011897:Random Allocation; D012201:Reward; D013395:Sucrose / Q000494:pharmacology; D013997:Time Factors
D009419:Nerve Tissue Proteins; D000439:Pentanols; D016372:RNA, Antisense; D009569:Nitric Oxide; D013395:Sucrose; C005716:amyl acetate; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I