title: Distinct Hippocampal Pathways Mediate Dissociable Roles of Context in Memory Retrieval.
abstract: Memories about sensory experiences are tightly linked to the context in which they were formed. Memory contextualization is fundamental for the selection of appropriate behavioral reactions needed for survival, yet the underlying neuronal circuits are poorly understood. By combining trans-synaptic viral tracing and optogenetic manipulation, we found that the ventral hippocampus (vHC) and the amygdala, two key brain structures encoding context and emotional experiences, interact via multiple parallel pathways. A projection from the vHC to the basal amygdala mediates fear behavior elicited by a conditioned context, whereas a parallel projection from a distinct subset of vHC neurons onto midbrain-projecting neurons in the central amygdala is necessary for context-dependent retrieval of cued fear memories. Our findings demonstrate that two fundamentally distinct roles of context in fear memory retrieval are processed by distinct vHC output pathways, thereby allowing for the formation of robust contextual fear memories while preserving context-dependent behavioral flexibility.
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors: Chun
authors: C
authors: Xu
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors: Sabine
authors: S
authors: Krabbe
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors: Jan
authors: J
authors: Gründemann
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, 4003 Basel, Switzerland.
authors: Paolo
authors: P
authors: Botta
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors: Jonathan P
authors: JP
authors: Fadok
authors: Systems Neurobiology Laboratories, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors: Fumitaka
authors: F
authors: Osakada
authors: Department of Internal Medicine 2, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors: Dieter
authors: D
authors: Saur
authors: CNC Program, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
authors: Benjamin F
authors: BF
authors: Grewe
authors: CNC Program, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
authors: Mark J
authors: MJ
authors: Schnitzer
authors: Systems Neurobiology Laboratories, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors: Edward M
authors: EM
authors: Callaway
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, 4003 Basel, Switzerland. Electronic address: andreas.luthi@fmi.ch.
authors: Andreas
authors: A
authors: Lüthi
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003213:Conditioning, Psychological; D055724:Electrophysiological Phenomena; D005239:Fear; D006624:Hippocampus / Q000502:physiology*; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways; D009474:Neurons / Q000166:cytology / Q000502:physiology; D062308:Optogenetics; D011820:Rabies virus / Q000235:genetics; D013569:Synapses
keywords: basal amygdala; central amygdala; contextual fear; fear conditioning; fear renewal; optogenetics; rabies-ArchT; trans-synaptic tracing; ventral hippocampus