Protein synthesis inhibitor phase shifts vasopressin rhythms in long-term suprachiasmatic cultures

1.The circadian rhythm of compound action potential frequency recorded from the isolated eye of Aplysia in culture medium and darkness was subjected to 6 h pulse treatments with either anisomycin, a protein synthesis inhibitor, or inactive derivatives of anisomycin. 2. Anisomycin caused phase-dependent phase shifts of the rhythm as expected from previous experiments, but none of the derivative molecules caused phase shifts or perturbed the rhythm. 3. Anisomycin inhibited eye-protein synthesis by 75% at the concentrations (10(−6) M) used in the phase shifting experiments but none of the derivatives inhibited synthesis. 4. Only those molecules that actually inhibited protein synthesis caused phase shifts of the clock, although the inactive derivatives differed from anisomycin by only an acetyl group. 5. The results strengthen the conclusion that the inhibition of protein synthesis caused by anisomycin is important in perturbing the timing of the circadian clock and not some other characteristic effect of the inhibitor molecule. Together with the results from other systems, these findings imply that the daily synthesis of protein is a general requirement for circadian clocks.

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Drug inhibition of memory formation in chickens II. Short-term memory

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1971.0075 ◽

1971 ◽

Vol 178 (1053) ◽

pp. 455-464 ◽

Cited By ~ 32

Keyword(s):

Protein Synthesis ◽

Sodium Pump ◽

Short Term Memory ◽

Memory Loss ◽

Protein Synthesis Inhibitor ◽

Protein Synthesis Inhibitors ◽

Short Term ◽

Synthesis Inhibitor ◽

Term Memory

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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Inhibitor of protein synthesis phase shifts a circadian pacemaker in mammalian SCN

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1988.255.6.r1055 ◽

1988 ◽

Vol 255 (6) ◽

pp. R1055-R1058

Author(s):

S. T. Inouye ◽

J. S. Takahashi ◽

F. Wollnik ◽

F. W. Turek

Keyword(s):

Protein Synthesis ◽

Circadian Rhythms ◽

Activity Rhythm ◽

Phase Shifts ◽

Protein Synthesis Inhibitor ◽

Circadian Pacemaker ◽

Synthesis Inhibitor ◽

Anatomic Site ◽

Site Of Action ◽

Inhibitor Of Protein Synthesis

The suprachiasmatic nucleus (SCN) of the hypothalamus contains a circadian pacemaker that regulates many circadian rhythms in mammals. Experimental work in microorganisms and invertebrates suggests that protein synthesis is required for the function of the circadian oscillator, and recent experiments in golden hamsters suggest an acute inhibition of protein synthesis can induce phase shifts in a mammalian circadian pacemaker. To determine whether protein synthesis in the SCN region is involved in the generation of circadian rhythms in mammals, a protein synthesis inhibitor, anisomycin, was microinjected into the SCN region, and the effect on the circadian rhythm of locomotor activity of hamsters was measured. A single injection of anisomycin into the SCN region induced phase shifts in the circadian activity rhythm that varied systematically as a function of the phase of injection within the circadian cycle. These results suggest that protein synthesis may be involved in the generation of circadian rhythms in mammals and that the anatomic site of action of anisomycin is within the hypothalamic suprachiasmatic region.

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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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Long-Lasting Effects of GABA Infusion Into the Cerebral Cortex of the Rat

Neural Plasticity ◽

10.1155/np.2000.1 ◽

2000 ◽

Vol 7 (1-2) ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Teresa Montiel ◽

Daniel Almeida ◽

Iván Arango ◽

Eduardo Calixto ◽

César Casasola ◽

...

Keyword(s):

Protein Synthesis ◽

Long Term Potentiation ◽

Information Storage ◽

Protein Synthesis Inhibitor ◽

Synthesis Inhibitor ◽

Receptor Stimulation ◽

Paroxysmal Activity ◽

The Brain

In electrophysiological terms, experimental models of durable information storage in the brain include long-term potentiation (LTP), long-term depression, and kindling. Protein synthesis correlates with these enduring processes. We propose a fourth example of long-lasting information storage in the brain, which we call the GABA-withdrawal syndrome (GWS). In rats, withdrawal of a chronic intracortical infusion of GABA, a ubiquitous inhibitory neurotransmitter, induced epileptogenesis at the infusion site. This overt GWS lasted for days. Anisomycin, a protein synthesis inhibitor, prevented the appearance of GWSin vivo. Hippocampal and neocortical slices showed a similar post-GABA hyperexcitabilityin vitroand an enhanced susceptibility to LTP induction. One to four months after the epileptic behavior disappeared, systemic administration of a subconvulsant dose of pentylenetetrazol produced the reappearance of paroxysmal activity. The long-lasting effects of tonicGABAAreceptor stimulation may be involved in long-term information storage processes at the cortical level, whereas the cessation ofGABAAreceptor stimulation may be involved in chronic pathological conditions, such as epilepsy. Furthermore, we propose that GWS may represent a common key factor in the addiction to GABAergic agents (for example, barbiturates, benzodiazepines, and ethanol). GWS represents a novel form of neurono-glial plasticity. The mechanisms of this phenomenon remain to be understood.

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