Gut vagal afferents differentially modulate innate anxiety and learned fear.
Vagal afferents are an important neuronal component of the gut-brain axis allowing bottom-up information flow from the viscera to the CNS. In addition to its role in ingestive behavior, vagal afferent signaling has been implicated modulating mood and affect, including distinct forms of anxiety and fear. Here, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on innate anxiety, conditioned fear, and neurochemical parameters in the limbic system. We found that compared with Sham controls, SDA rats consistently displayed reduced innate anxiety-like behavior in three procedures commonly used in preclinical rodent models of anxiety, namely the elevated plus maze test, open field test, and food neophobia test. On the other hand, SDA rats exhibited increased expression of auditory-cued fear conditioning, which specifically emerged as attenuated extinction of conditioned fear during the tone re-exposure test. The behavioral manifestations in SDA rats were associated with region-dependent changes in noradrenaline and GABA levels in key areas of the limbic system, but not with functional alterations in the hypothalamus-pituitary-adrenal grand stress. Our study demonstrates that innate anxiety and learned fear are both subjected to visceral modulation through abdominal vagal afferents, possibly via changing limbic neurotransmitter systems. These data add further weight to theories emphasizing an important role of afferent visceral signals in the regulation of emotional behavior.
Physiology and Behavior Laboratory, ETH Zurich, 8603 Schwerzenbach, Switzerland and.
Melanie
M
Klarer
Physiology and Behavior Laboratory, ETH Zurich, 8603 Schwerzenbach, Switzerland and.
Myrtha
M
Arnold
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technical University Dresden, 01307 Dresden, Germany.
Lydia
L
Günther
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technical University Dresden, 01307 Dresden, Germany.
Christine
C
Winter
Physiology and Behavior Laboratory, ETH Zurich, 8603 Schwerzenbach, Switzerland and.
Wolfgang
W
Langhans
Physiology and Behavior Laboratory, ETH Zurich, 8603 Schwerzenbach, Switzerland and urmeyer@ethz.ch.
Urs
U
Meyer
D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D004435:Eating / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000502:physiology* / Q000523:psychology; D007839:Functional Laterality; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000294:innervation*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D018377:Neurotransmitter Agents; D012844:Sincalide
GABA; anxiety; fear; gut feelings; vagus nerve