RESUMEN
The emission of 50 kHz frequency-modulated ultrasonic vocalizations (FM USVs) in rats has been associated with positive affective states, while a decrease in FM USVs has been associated with anxiety-like states. We tested the hypothesis in male Sprague-Dawley rats that FM USVs would complement measures of aversive memories (decrease in FM USVs) in a conditioned fear task in which we examined extinction or reconsolidation disruption. In Experiment 1, rats were fear conditioned using low-level footshock followed by extinction while monitoring freezing and FM USVs. In Experiment 2, rats were fear conditioned, the alpha-1 antagonist prazosin was used to disrupt reconsolidation of memory, and freezing and FM USVs were measured. Rats fear conditioned with low-level shock showed minimal freezing that rapidly extinguished, despite a persistent decrease in FM USVs throughout extinction. Prazosin reduced freezing in a memory reactivation-dependent manner as expected, but the reduction in FM USVs after fear conditioning remained decreased, suggesting that an affective component of memory was not impacted by prazosin. These findings indicate that FM USVs may be used as an index of fear- or anxiety-like memory, and their measurement could benefit pre-clinical animal models for assessing reduction of aversive memories.
Asunto(s)
Miedo , Memoria , Vocalización Animal , Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Animales , Reacción de Prevención/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Electrochoque , Extinción Psicológica/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Consolidación de la Memoria/efectos de los fármacos , Prazosina/administración & dosificación , Ratas Sprague-Dawley , UltrasonidoRESUMEN
Lymnaea stagnalis provides an excellent model system for studying memory because these snails have a well-described set of neurons, a single one of which controls expression of long-term memory of operantly conditioned respiratory behavior. We have shown that several different manipulations, including pre-training exposure to serotonin (5-HT) or methamphetamine, submersion of snails after training to prevent memory interference, and exposure to effluent from predatory crayfish (CE), enhance memory persistence. Changes in DNA methylation underlie formation of strong memories in mammals and 5-HT-enhanced long-term facilitation in Aplysia. Here we determined the impact of the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-AZA; 87 µmol l(-1)), on enhanced memory persistence by all four manipulations. We found that 5-HT (100 µmol l(-1)) enhanced memory persistence, which was blocked by 5-AZA pretreatment. Snails pre-exposed to 3.3 µmol l(-1) Meth 4 h prior to training demonstrated memory 72 h later, which was not present in controls. This memory-enhancing effect was blocked by pre-treatment with 87 µmol l(-1) 5-AZA. Similarly, submersion to prevent interference learning as well as training in CE produced memory that was not present in controls, and these effects were blocked by pre-treatment with 87 µmol l(-1) 5-AZA. In contrast, 5-AZA injection did not alter expression of normal (non-enhanced) memory, suggesting that these four stimuli enhance memory persistence by increasing DNA methyltransferase activity, which, in turn, increases expression of memory-enhancing genes and/or inhibits memory suppressor genes. These studies lay important groundwork for delineating gene methylation changes that are common to persistent memory produced by different stimuli.