Memory impairment correlates closely with cycloheximide dose and degree of inhibition of protein synthesis

Quinton, Elton E.; Kramarcy, Neal R.

doi:10.1016/0006-8993(77)90041-5

Cited by 50 publications

(19 citation statements)

References 7 publications

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“…In our setup, PSI was reduced to 72% by 24 hr and was fully released after 48 hr. Maximum levels of PSI measured here were below the threshold of 90% postulated by Davis and Squire (1984) for PSI to impair memory consolidation, but they were above the 80% level proposed by others (Quinton and Kramarcy, 1977). This may be related to the timing of the measurement, which may have missed the peak effect at 30 min; more likely, it is a consequence of the large sampling area and thereby inclusion of tissue with low ANI concentration and low protein synthesis inhibition.…”

Section: Discussioncontrasting

confidence: 65%

Motor Skill Learning Depends on Protein Synthesis in Motor Cortex after Training

Luft¹,

Buitrago²,

Ringer³

et al. 2004

J. Neurosci.

137

104

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The role of protein synthesis in memory consolidation is well established for hippocampus-dependent learning and synaptic plasticity. Whether protein synthesis is required for motor skill learning is unknown. We hypothesized that skill learning is interrupted by protein synthesis inhibition (PSI). We intended to test whether local protein synthesis in motor cortex or cerebellum is required during skill acquisition and consolidation. Anisomycin (ANI; 100 g/l in 1 l of PBS) injected into motor cortex, posterior parietal cortex, or cerebellum produced 84.0 Ϯ 1.44% (mean Ϯ SEM), 85.9 Ϯ 2.31%, and 87.3 Ϯ 0.17% of PSI 60 min after administration, respectively. In motor cortex, protein synthesis was still reduced at 24 hr (72.0 Ϯ 4.68% PSI) but normalized at 48 hr after a second injection given 24 hr after the first. To test for the effects of PSI on learning of a skilled reaching task, ANI was injected into motor cortex contralateral to the trained limb or into ipsilateral cerebellum immediately after daily training sessions 1 and 2. Two control groups received motor cortex injections of vehicle or ANI injections into contralateral parietal cortex. Control and cerebellar animals showed a sigmoid learning curve, which plateaued after day 4. PSI in motor cortex significantly reduced learning during days 1-4. Thereafter, when protein synthesis normalized, learning was reinitiated. ANI injections into motor cortex did not induce a motor deficit, because animals injected during the performance plateau did not deteriorate. This demonstrates that motor skill learning depends on de novo synthesis of proteins in motor cortex after training.

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Section: Discussioncontrasting

confidence: 65%

Motor Skill Learning Depends on Protein Synthesis in Motor Cortex after Training

Luft¹,

Buitrago²,

Ringer³

et al. 2004

J. Neurosci.

137

104

View full text Add to dashboard Cite

show abstract

“…More importantly, similarities in the role of new protein synthesis in long-term memory and in the induction of LTP would provide convergent evidence supporting a role for LTP in learning and memory processes. In the behavioral literature, a critical level of protein synthesis is required for the formation of long-term memory (Bennett et al, 1977;Quinton and Kramarcy, 1977). An amnestic effect was observed after the administration of either anisomycin or cycloheximide, when the inhibition protein synthesis was over 80%.…”

Section: Discussionmentioning

confidence: 99%

Protein Synthesis Inhibition Blocks the Induction of Mossy Fiber Long-Term PotentiationIn Vivo

et al. 2000

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Protein synthesis inhibitors block the maintenance of NMDA receptor-dependent long-term potentiation (LTP) both in vivo and in vitro. Protein synthesis inhibitors block mossy fiber(MF) LTP maintenance in vitro, but little is known about the effect of protein synthesis inhibitors on either induction or maintenance in MF-LTP in vivo. Here we study the role of protein synthesis in the induction of long-term potentiation at the mossy fiber-CA3 hippocampal synapse in vivo in anesthetized rats. The protein synthesis inhibitor anisomycin was administered at different doses (0.04, 10, or 40 nmol) into area CA3 15 min before delivering high-frequency stimulation (two times at 100 Hz, 1 sec). Anisomycin blocked MF-LTP induction in a dose-dependent manner; both 40 and 10 nmol blocked MF-LTP induction, but a lower dose of 0.04 nmol was without effect. The inhibitory effect of anisomycin on protein synthesis was determined by measuring the incorporation of [35 S]methionine into the newly synthesized proteins. Percentages of protein synthesis inhibition were determined by comparing [35 S] incorporation of anisomycin-treated samples with vehicle controls. Doses of 0.04, 10, or 40 nmol of anisomycin produced 21, 82, or 83% inhibition of [35 S]methionine incorporation, respectively. The effect of anisomycin was verified using a single dose of the protein synthesis inhibitor cycloheximide (40 nmol). Cycloheximide also blocked MF-LTP induction. These results suggest that protein synthesis plays an important role in the induction of mossy fiber long-term potentiation in vivo.

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“…The dosages used in the present study were deduced from literature data showing that ANI and EME efficiently inhibit protein synthesis in various species and brain structures (for references, see Introduction) and that a level of 80% protein-synthesis inhibition is critical for amnesic effects to occur (Flood et al 1973;Quinton and Kramarcy 1977). Specifically, the highest dose (113 mM) of ANI was chosen based on previously published studies showing 80% suppression of protein synthesis in rat cerebral cortex and hippocampus after injections of 100 µg ANI per hemisphere (Rosenblum et al 1993;Meiri and Rosenblum 1998).…”

Section: Surgical Procedures and Intracortical Injectionsmentioning

confidence: 99%

Memory Consolidation for the Discrimination of Frequency-Modulated Tones in Mongolian Gerbils Is Sensitive to Protein-Synthesis Inhibitors Applied to the Auditory Cortex

Kraus¹,

Schicknick²,

Wetzel³

et al. 2002

Learn. Mem.

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Differential conditioning of Mongolian gerbils to linearly frequency-modulated tones (FM) has recently received experimental attention. In the study of the role of cerebral protein synthesis for FM discrimination memory, gerbils received post-training bilateral injections of anisomycin into the auditory cortex under light halothane anesthesia. Compared with saline-treated controls, anisomycin-treated gerbils showed a discrimination decrement during the subsequent three days of training. They markedly improved their performance within training sessions, but started each session at low levels. When repeatedly trained gerbils received post-session injections of anisomycin, discrimination performance during subsequent sessions was similar to the pre-injection performance, indicating that retention, retrieval, reconsolidation, and expression of the established reaction were not affected. However, the improvement of a partially established discrimination reaction was impaired after this treatment. Intracortical injections of emetine confirmed this finding. Neither drug affected FM discrimination learning when given several days before the initial training. Our results suggest that protein-synthesis inhibitors applied to the auditory cortex of gerbils during the post-acquisition phase interfered with learning and memory-related aspects of FM processing. The resulting deficit was evident for a number of post-injection training days. This effect was probably due to impaired consolidation, i.e., processes required for long-term stabilization or retrieval of the memory trace while leaving short-term memory intact.

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Memory impairment correlates closely with cycloheximide dose and degree of inhibition of protein synthesis

Cited by 50 publications

References 7 publications

Motor Skill Learning Depends on Protein Synthesis in Motor Cortex after Training

Motor Skill Learning Depends on Protein Synthesis in Motor Cortex after Training

Protein Synthesis Inhibition Blocks the Induction of Mossy Fiber Long-Term PotentiationIn Vivo

Memory Consolidation for the Discrimination of Frequency-Modulated Tones in Mongolian Gerbils Is Sensitive to Protein-Synthesis Inhibitors Applied to the Auditory Cortex

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