Innate Predator Odor Aversion Driven by Parallel Olfactory Subsystems that Converge in the Ventromedial Hypothalamus.
The existence of innate predator aversion evoked by predator-derived chemostimuli called kairomones offers a strong selective advantage for potential prey animals. However, it is unclear how chemically diverse kairomones can elicit similar avoidance behaviors. Using a combination of behavioral analyses and single-cell Ca(2+) imaging in wild-type and gene-targeted mice, we show that innate predator-evoked avoidance is driven by parallel, non-redundant processing of volatile and nonvolatile kairomones through the activation of multiple olfactory subsystems including the Grueneberg ganglion, the vomeronasal organ, and chemosensory neurons within the main olfactory epithelium. Perturbation of chemosensory responses in specific subsystems through disruption of genes encoding key sensory transduction proteins (Cnga3, Gnao1) or by surgical axotomy abolished avoidance behaviors and/or cellular Ca(2+) responses to different predator odors. Stimulation of these different subsystems resulted in the activation of widely distributed target regions in the olfactory bulb, as assessed by c-Fos expression. However, in each case, this c-Fos increase was observed within the same subnuclei of the medial amygdala and ventromedial hypothalamus, regions implicated in fear, anxiety, and defensive behaviors. Thus, the mammalian olfactory system has evolved multiple, parallel mechanisms for kairomone detection that converge in the brain to facilitate a common behavioral response. Our findings provide significant insights into the genetic substrates and circuit logic of predator-driven innate aversion and may serve as a valuable model for studying instinctive fear and human emotional and panic disorders.
Department of Physiology and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421 Homburg, Germany.
Anabel
A
Pérez-Gómez
Department of Physiology and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421 Homburg, Germany.
Katherin
K
Bleymehl
Department of Physiology and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421 Homburg, Germany.
Benjamin
B
Stein
Department of Physiology and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421 Homburg, Germany.
Martina
M
Pyrski
Laboratory of Neurobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Lutz
L
Birnbaumer
Department of Pharmacology and Therapeutics, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, and Center for Smell and Taste, University of Florida, Gainesville, FL 32610, USA.
Steven D
SD
Munger
Department of Physiology and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421 Homburg, Germany.
Trese
T
Leinders-Zufall
Department of Physiology and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421 Homburg, Germany. Electronic address: frank.zufall@uks.eu.
Frank
F
Zufall
Department of Physiology and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421 Homburg, Germany.
Pablo
P
Chamero
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism; D005724:Ganglia / Q000378:metabolism; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009812:Odorants; D009830:Olfactory Bulb / Q000502:physiology*; D010627:Phenethylamines; D010675:Pheromones; D011235:Predatory Behavior; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D015398:Signal Transduction; D019147:Vomeronasal Organ / Q000502:physiology
C518237:Cnga3 protein, mouse; D054815:Cyclic Nucleotide-Gated Cation Channels; D010627:Phenethylamines; D010675:Pheromones; D016760:Proto-Oncogene Proteins c-fos; C029261:phenethylamine; D019206:GTP-Binding Protein alpha Subunits, Gi-Go