Inactivation of the dorsolateral periaqueductal gray matter impairs the promoting influence of stress on fear memory during retrieval
Exposure to stressful conditions induces long-lasting neurobiological changes in selected brain areas, which could be associated with the emergence of negative emotional responses. Moreover, the interaction of a stressful experience and the retrieval of an established fear memory trace enhance both fear expression and fear retention. Related to this, the stimulation of the dorsolateral part of the mesencephalic periaqueductal gray matter (dlPAG) prior to retrieval potentiates a fear memory trace previously acquired. Therefore, the question that arises is whether the dlPAG mediates the increased fear expression and fear retention after retrieval. Rats were subjected to a contextual fear conditioning paradigm using a single footshock, and 1 day later, rats were subjected to a stressful situation. As previously reported, there was an increase of freezing response only in those rodents that were re-exposed to the associated context at 1 and 5 days after stress exposure. Muscimol intra-dlPAG prior to the restraint event prevented such increase. Conversely, Muscimol intra-dlPAG infusion immediately after the stress experience had no effect on the resulting fear memory. When the neuroendocrine response to stress was explored, intra-dlPAG infusion of muscimol prior to stress decreased Fos expression in the paraventricular nucleus and serum corticosterone levels. Moreover, this treatment prevented the enhancement of the density of hippocampal “mature” spines associated with fear memory. In conclusion, the present results suggest that the dlPAG is a key neural site for the negative valence instruction necessary to modulate the promoting influence of stress on fear memory.
KeywordsFear memory Stress Retrieval Periaqueductal gray matter Valence instruction
This research was supported by FAPESP, CAPES, and CNPq from which MG and EP received a post-doctoral fellowship and APC and NSC a research fellowship.
Compliance with ethical standards
Conflict of interest
We have no commercial associations which impact on this work. Funding for this study was provided by Brazilian public agencies CAPES, CNPq, and FAPESP; they had no further role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
The current research was approved by the Federal University of Santa Catarina, Animal Ethics Committee (23080.0055752/2006-64/UFSC), and was performed in accordance with the Brazilian Society of Neuroscience and Behavior Guidelines for the Care and Use of Laboratory Animals.
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