Critical time window for NO-cGMP-dependent long-term memory formation after one-trial appetitive conditioning

Kemenes, Ildikó, Kemenes, György, Andrew, Richard J, Benjamin, Paul R and O'Shea, Michael (2002) Critical time window for NO-cGMP-dependent long-term memory formation after one-trial appetitive conditioning. Journal of Neuroscience, 22 (4). pp. 1414-1425. ISSN 0270-6474

PDF - Published Version
Download (276kB) | Preview


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.

Item Type: Article
Additional Information: 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.
Schools and Departments: School of Life Sciences > Neuroscience
Depositing User: Ildiko Kemenes
Date Deposited: 06 Feb 2012 21:28
Last Modified: 03 Jul 2019 00:47

View download statistics for this item

📧 Request an update