Learning & Memory · 1999 · 404 citations · 47 references
MedicineNeurosciencePharmacologyMemoryMolecular NeurobiologyNeuropharmacologyFear CircuitsLong-term PotentiationMemory ConsolidationNeural Basis Of MemoryNeuromodulationAuditory Memory ConsolidationContextual Fear MemoryFear Conditioning AssessmentFear LearningFear ModulationPavlovian Fear ConditioningPharmacological DisruptionProtein Synthesis-dependent Consolidation
Fear conditioning has been extensively studied, yet the molecular mechanisms underlying fear memory consolidation remain poorly understood, despite evidence that long‑term potentiation occurs in relevant pathways and that fear conditioning induces changes similar to LTP. The study aimed to determine whether blocking protein synthesis, PKA, or MAP kinase activity interferes with fear conditioning consolidation. Rats received intraventricular injections of anisomycin, Rp‑cAMPS, or PD098059 before conditioning, and their contextual and auditory fear memory was tested after one hour and 24 hours. The drugs selectively disrupted long‑term contextual and auditory fear memory while sparing short‑term memory, an effect attributed to impaired consolidation rather than altered fear expression, indicating that fear conditioning and LTP share common molecular mechanisms.
Fear conditioning has received extensive experimental attention. However, little is known about the molecular mechanisms that underlie fear memory consolidation. Previous studies have shown that long-term potentiation (LTP) exists in pathways known to be relevant to fear conditioning and that fear conditioning modifies neural processing in these pathways in a manner similar to LTP induction. The present experiments examined whether inhibition of protein synthesis, PKA, and MAP kinase activity, treatments that block LTP, also interfere with the consolidation of fear conditioning. Rats were injected intraventricularly with Anisomycin (100 or 300 microg), Rp-cAMPS (90 or 180 microg), or PD098059 (1 or 3 microg) prior to conditioning and assessed for retention of contextual and auditory fear memory both within an hour and 24 hr later. Results indicated that injection of these compounds selectively interfered with long-term memory for contextual and auditory fear, while leaving short-term memory intact. Additional control groups indicated that this effect was likely due to impaired memory consolidation rather than to nonspecific effects of the drugs on fear expression. Results suggest that fear conditioning and LTP may share common molecular mechanisms.
47