Neurosilence: profound suppression of neural activity following intracerebral administration of the protein synthesis inhibitor anisomycin

• Published in: The Journal of neuroscience 2012-02, Vol.32 (7), p.2377-2387
• Main Authors: Sharma, Arjun V, Nargang, Frank E, Dickson, Clayton T
• Format: Article
• Language: English
• Subjects: Animals; Anisomycin - administration & dosage; Anti-Bacterial Agents - administration & dosage; Evoked Potentials - drug effects; Evoked Potentials - physiology; Hippocampus - drug effects; Hippocampus - physiology; Injections, Intraventricular; Male; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neurons - drug effects; Neurons - physiology; Protein Biosynthesis - drug effects; Protein Biosynthesis - physiology; Protein Synthesis Inhibitors - administration & dosage; Rats; Rats, Sprague-Dawley
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.3543-11.2012

Early in their formation, memories are thought to be labile, requiring a process called consolidation to give them near-permanent stability. Evidence for consolidation as an active and biologically separate mnemonic process has been established through posttraining manipulations of the brain that promote or disrupt subsequent retrieval. Consolidation is thought to be ultimately mediated via protein synthesis since translational inhibitors such as anisomycin disrupt subsequent memory when administered in a critical time window just following initial learning. However, when applied intracerebrally, they may induce additional neural disturbances. Here, we report that intrahippocampal microinfusions of anisomycin in urethane-anesthetized rats at dosages previously used in memory consolidation studies strongly suppressed (and in some cases abolished) spontaneous and evoked local field potentials (and associated extracellular current flow) as well as multiunit activity. These effects were not coupled to the production of pathological electrographic activity nor were they due to cell death. However, the amount of suppression was correlated with the degree of protein synthesis inhibition as measured by autoradiography and was also observed with cycloheximide, another translational inhibitor. Our results suggest that (1) the amnestic effects of protein synthesis inhibitors are confounded by neural silencing and that (2) intact protein synthesis is crucial for neural signaling itself.