Enhanced inhibitory avoidance learning prevents the long-term memory-impairing effects of cycloheximide, a protein synthesis inhibitor

1. Memory in day-old-chickens during the first few hours after learning can be made to decline by the prior intracranial injection of two classes of drugs. 2. Sodium pump inhibitors in increasing doses cause increasingly rapid loss of memory. 3. Protein synthesis inhibitors in increasing doses attain a maximum potency in causing memory decline and the rate may not be further accelerated by higher doses. 4. Adding a sodium pump inhibitor to the inhibition of protein synthesis increases memory loss. 5. Adding a protein synthesis inhibitor to a sodium pump inhibitor causes no further loss. 6. Therefore within a few minutes of learning a short-term memory of limited time span but independent of protein synthesis becomes supplemented and eventually replaced by a long-term storage requiring protein synthesis. The amount of long-term store is set by the amount of short-term memory. 7. The short-term store could be directly dependent on post-activation enhancement of Na + extrusion from neurons. Some physiological mechanisms by which this could be achieved and how this might activate protein synthesis are discussed.

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Different Training Procedures Recruit Either One or Two Critical Periods for Contextual Memory Consolidation, Each of Which Requires Protein Synthesis and PKA

Learning & Memory ◽

10.1101/lm.5.4.365 ◽

1998 ◽

Vol 5 (4) ◽

pp. 365-374 ◽

Cited By ~ 23

Author(s):

Roussoudan Bourtchouladze ◽

Ted Abel ◽

Nathaniel Berman ◽

Rachael Gordon ◽

Kyle Lapidus ◽

...

Keyword(s):

Protein Synthesis ◽

Time Course ◽

Contextual Fear Conditioning ◽

Long Term Memory ◽

Protein Synthesis Inhibitor ◽

Critical Periods ◽

Synthesis Inhibitor ◽

Contextual Memory ◽

Contextual Fear

We have used a combined genetic and pharmacological approach to define the time course of the requirement for protein kinase A (PKA) and protein synthesis in long-term memory for contextual fear conditioning in mice. The time course of amnesia in transgenic mice that express R(AB) and have genetically reduced PKA activity in the hippocampus parallels that observed both in mice treated with inhibitors of PKA and mice treated with inhibitors of protein synthesis. This PKA- and protein synthesis-dependent memory develops between 1 hr and 3 hr after training. By injecting the protein synthesis inhibitor anisomycin or the PKA inhibitor Rp-cAMPs at various times after training, we find that depending on the nature of training, contextual memory has either one or two brief consolidation periods requiring synthesis of new proteins, and each of these also requires PKA. Weak training shows two time periods of sensitivity to inhibitors of protein synthesis and PKA, whereas stronger training exhibits only one. These studies underscore the parallel dependence of long-term contextual memory on protein synthesis and PKA and suggest that different training protocols may recruit a common signaling pathway in distinct ways.

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