<p>BACKGROUND: Traumatic experiences, such as conditioned threat, are coded as enduring memories that are frequently subject to generalization, which is characterized by (re-) expression of fear in safe environments. However, the neurobiological mechanisms underlying threat generalization after a traumatic experience and the role of stress hormones in this process remain poorly understood. METHODS: We examined the influence of glucocorticoid hormones on the strength and specificity of conditioned fear memory at the level of sparsely distributed dentate gyrus (DG) engram cells in male mice. RESULTS: We found that elevating glucocorticoid hormones after fear conditioning induces a generalized contextual fear response. This was accompanied by a selective and persistent increase in the excitability and number of activated DG granule cells. Selective chemogenetic suppression of these sparse cells in the DG prevented glucocorticoid-induced fear generalization and restored contextual memory specificity, while leaving expression of auditory fear memory unaffected. CONCLUSIONS: These results implicate the sparse ensemble of DG engram cells as a critical cellular substrate underlying fear generalization induced by glucocorticoid stress hormones.</p>

doi.org/10.1016/j.biopsych.2021.04.010, hdl.handle.net/1765/136759
Biological Psychiatry
Erasmus MC: University Medical Center Rotterdam

Sylvie L. Lesuis, Niek Brosens, Nathalie Immerzeel, Rolinka J. van der Loo, Miodrag Mitrić, Pascal Bielefeld, … Harm J. Krugers. (2021). Glucocorticoids Promote Fear Generalization by Increasing the Size of a Dentate Gyrus Engram Cell Population. Biological Psychiatry, 90(7), 494–504. doi:10.1016/j.biopsych.2021.04.010