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Critical time window for NO-cGMP-dependent long-term memory formation after one-trial appetitive conditioning
journal contribution
posted on 2023-06-08, 10:05 authored by Ildiko KemenesIldiko Kemenes, George KemenesGeorge Kemenes, Richard J Andrew, Paul R Benjamin, Michael O'SheaThe 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.
History
Publication status
- Published
File Version
- Published version
Journal
Journal of NeuroscienceISSN
0270-6474Publisher
Society for NeuroscienceIssue
4Volume
22Page range
1414-1425Pages
12.0Department affiliated with
- Neuroscience Publications
Notes
MO initiated the NO project, designed the experiments and wrote the paper. This paper establishes that NO-cGMP signalling is required in the early phase of memory formation. Importantly, it formed the foundation for subsequent research on the key molecular mechanisms of long term memory formation in this model system.Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06First Open Access (FOA) Date
2016-03-22First Compliant Deposit (FCD) Date
2016-08-17Usage metrics
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