title: Prenatal Stress Produces Persistence of Remote Memory and Disrupts Functional Connectivity in the Hippocampal-Prefrontal Cortex Axis.
abstract: Prenatal stress is a risk factor for the development of neuropsychiatric disorders, many of which are commonly characterized by an increased persistence of aversive remote memory. Here, we addressed the effect of prenatal stress on both memory consolidation and functional connectivity in the hippocampal-prefrontal cortex axis, a dynamical interplay that is critical for mnemonic processing. Pregnant mice of the C57BL6 strain were subjected to restraint stressed during the last week of pregnancy, and male offspring were behaviorally tested at adulthood for recent and remote spatial memory performance in the Barnes Maze test under an aversive context. Prenatal stress did not affect the acquisition or recall of recent memory. In contrast, it produced the persistence of remote spatial memory. Memory persistence was not associated with alterations in major network rhythms, such as hippocampal sharp-wave ripples (SWRs) or neocortical spindles. Instead, it was associated with a large decrease in the basal discharge activity of identified principal neurons in the medial prefrontal cortex (mPFC) as measured in urethane anesthetized mice. Furthermore, functional connectivity was disrupted, as the temporal coupling between neuronal discharge in the mPFC and hippocampal SWRs was decreased by prenatal stress. These results could be relevant to understand the biological basis of the persistence of aversive remote memories in stress-related disorders.
authors.affiliation: Departamento de Psiquiatría, Facultad de Medicina, Centro Interdisciplinario de Neurociencia, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Negrón-Oyarzo
authors.affiliation: Departamento de Psiquiatría, Facultad de Medicina, Centro Interdisciplinario de Neurociencia, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: David
authors.initials: D
authors.lastname: Neira
authors.affiliation: Departamento de Psiquiatría, Facultad de Medicina, Centro Interdisciplinario de Neurociencia, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Nelson
authors.initials: N
authors.lastname: Espinosa
authors.affiliation: Departamento de Psiquiatría, Facultad de Medicina, Centro Interdisciplinario de Neurociencia, Pontificia Universidad Católica de Chile, Santiago, Chile Fundación San Juan de Dios, Barcelona, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Fuentealba
authors.affiliation: Departamento de Psiquiatría, Facultad de Medicina, Centro Interdisciplinario de Neurociencia, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Aboitiz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004594:Electrophysiology; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning; D008564:Membrane Potentials / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology*; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000502:physiology; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D013223:Statistics as Topic; D013315:Stress, Psychological / Q000150:complications* / Q000473:pathology
keywords: medial prefrontal cortex; memory; prenatal stress