Distinct Contributions of Median Raphe Nucleus to ContextualFear Conditioning and Fear-Potentiated Startle

摘要

Ascending 5-HT projections from the median raphe nucleus (MRN), probably to the hippocampus, are implicated in the acquisition of contextual fear (background stimuli), as assessed by freezing behavior. Foreground cues like light, used as a conditioned stimulus (CS) in classical fear conditioning, also cause freezing through thalamic transmission to the amygdala. As the MRN projects to the hippocampus and amygdala, the role of this raphe nucleus in fear conditioning to explicit cues remains to be explained. Here we analyzed the behavior of rats with MRN electrolytic lesions in a contextual conditioning situation and in a fear-potentiated startle procedure. The animals received MRN electrolytic lesions either before or on the day after two consecutive trainingsessions in which they were submitted to 10conditioning trials, each in an experimentalchamber (same context) where they. receivedfoot-shocks (0.6 mA, 1 sec) paired to a 4-seclight CS. Seven to ten days later, the animalswere submitted to testing sessions for assessingconditioned fear when they were placed for fiveshocks, and the duration of contextual freezingwas recorded. The animals were then submittedto a fear-potentiated startle in response to a 4-seclight-CS, followed by white noise (100 dB, 50 ms). Control rats (sham) tested in the samecontext showed more freezing than did ratswith pre- or post-training MRN lesions. Startlewas clearly potentiated in the presence of light CS in the sham-lesioned animals. Whereas pretraininglesions reduced both freezing and fear-potentiatedstartle, the post-training lesionsreduced only freezing to context, withoutchanging the fear-potentiated startle. In asecond experiment, neurotoxic lesions of theMRN with local injections of N-methyl-D-aspartateor the activation of 5-HT1A somatodendriticauto-receptors of the MRN bymicroinjections of the 5-HT1A receptor agonist8-hydroxy- 2-(di-n-propylamino)tetralin (8-OH-DPAT)before the training sessions also reducedthe amount of freezing and the fear-potentiatedstartle. Freezing is a prominent response ofcontextual fear conditioning, but does not seemto be crucial for the enhancement of the startlereflex by explicit aversive cues. As fear-potentiatedstartle may be produced in posttraininglesioned rats that are unable to freezeto fear contextual stimuli, dissociable systemsseem to be recruited in each condition. Thus,contextual fear and fear-potentiated startle areconveyed by distinct 5-HT-mediated circuits ofthe MRN.