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The Journal of Neuroscience, February 15, 2002, 22(4):1414-1425
Critical Time-Window for NO-cGMP-Dependent Long-Term Memory
Formation after One-Trial Appetitive Conditioning
Ildikó
Kemenes,
György
Kemenes,
Richard J.
Andrew,
Paul R.
Benjamin, and
Michael
O'Shea
Sussex Centre for Neuroscience, School of Biological Sciences,
University of Sussex, Falmer, Brighton, United Kingdom, BN1 9QG
The nitric oxide (NO)-cGMP signaling pathway is implicated in an
increasing number of experimental models of plasticity. Here, in a
behavioral analysis using one-trial appetitive associative conditioning, we show that there is an obligatory requirement for this
pathway in the formation of long-term memory (LTM). Moreover, we
demonstrate that this requirement lasts for a critical period of ~5
hr after training. Specifically, we trained intact specimens of the
snail Lymnaea stagnalis in a single conditioning trial using a conditioned stimulus, amyl-acetate, paired with a salient unconditioned stimulus, sucrose, for feeding. Long-term associative memory induced by a single associative trial was demonstrated at 24 hr
and shown to last at least 14 d after training. Tests for LTM and
its dependence on NO were performed routinely 24 hr after training. The
critical period when NO was needed for memory formation was established
by transiently depleting it from the animals at a series of time points
after training by the injection of the NO-scavenger
2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl 3-oxide (PTIO).By
blocking the activity of NO synthase and soluble guanylyl cyclase
enzymes after training, we provided further evidence that LTM formation
depends on an intact NO-cGMP pathway. An electrophysiological correlate
of LTM was also blocked by PTIO, showing that the dependence of LTM on
NO is amenable to analysis at the cellular level in vitro. This represents the first demonstration that associative memory formation after single-trial appetitive classical conditioning is dependent on an intact NO-cGMP signaling pathway.
Key words:
one-trial classical conditioning; long-term memory; critical period; nitric oxide; cGMP; Lymnaea
Copyright © 2002 Society for Neuroscience 0270-6474/02/2241414-12$05.00/0
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