title: Direct dorsal hippocampal-prelimbic cortex connections strengthen fear memories.
abstract: The ability to regulate the consolidation and strengthening of memories for threatening experiences is critical for mental health, and its dysregulation may lead to psychopathologies. Re-exposure to the context in which the threat was experienced can either increase or decrease fear response through distinct processes known, respectively, as reconsolidation or extinction. Using a context retrieval-dependent memory-enhancement model in rats, we report that memory strengthens through activation of direct projections from dorsal hippocampus to prelimbic (PL) cortex and activation of critical PL molecular mechanisms that are not required for extinction. Furthermore, while sustained PL brain-derived neurotrophic factor (BDNF) expression is required for memory consolidation, retrieval engages PL BDNF to regulate excitatory and inhibitory synaptic proteins neuroligin 1 and neuroligin 2, which promote memory strengthening while inhibiting extinction. Thus, context retrieval-mediated fear-memory enhancement results from a concerted action of mechanisms that strengthen memory through reconsolidation while suppressing extinction.
authors.affiliation: Center for Neural Science, New York University, New York, New York, USA.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Ye
authors.affiliation: Center for Neural Science, New York University, New York, New York, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Kapeller-Libermann
authors.affiliation: Center for Neural Science, New York University, New York, New York, USA.
authors.forename: Alessio
authors.initials: A
authors.lastname: Travaglia
authors.affiliation: Center for Neural Science, New York University, New York, New York, USA.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Inda
authors.affiliation: Center for Neural Science, New York University, New York, New York, USA.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Alberini
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D011939:Mental Recall / Q000502:physiology*; D023421:Models, Animal; D017397:Prefrontal Cortex / Q000502:physiology*; D020318:Rats, Long-Evans
chemical_list: D019208:Brain-Derived Neurotrophic Factor