TY  - JOUR
A1  - Genheimer, Hannah
A1  - Andreatta, Marta
A1  - Asan, Esther
A1  - Pauli, Paul
T1  - Reinstatement of contextual conditioned anxiety in virtual reality and the effects of transcutaneous vagus nerve stimulation in humans
JF  - Scientific Reports
N2  - Since exposure therapy for anxiety disorders incorporates extinction of contextual anxiety, relapses may be due to reinstatement processes. Animal research demonstrated more stable extinction memory and less anxiety relapse due to vagus nerve stimulation (VNS). We report a valid human three-day context conditioning, extinction and return of anxiety protocol, which we used to examine effects of transcutaneous VNS (tVNS). Seventy-five healthy participants received electric stimuli (unconditioned stimuli, US) during acquisition (Day1) when guided through one virtual office (anxiety context, CTX+) but never in another (safety context, CTX−). During extinction (Day2), participants received tVNS, sham, or no stimulation and revisited both contexts without US delivery. On Day3, participants received three USs for reinstatement followed by a test phase. Successful acquisition, i.e. startle potentiation, lower valence, higher arousal, anxiety and contingency ratings in CTX+ versus CTX−, the disappearance of these effects during extinction, and successful reinstatement indicate validity of this paradigm. Interestingly, we found generalized reinstatement in startle responses and differential reinstatement in valence ratings. Altogether, our protocol serves as valid conditioning paradigm. Reinstatement effects indicate different anxiety networks underlying physiological versus verbal responses. However, tVNS did neither affect extinction nor reinstatement, which asks for validation and improvement of the stimulation protocol.
KW  - psychology
KW  - vagus nerve stimulation
KW  - contextual anxiety
KW  - fear conditioning
KW  - extinction
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169892
VL  - 7
IS  - 17886
ER  - 
TY  - JOUR
A1  - Scholz, Nicole
A1  - Guan, Chonglin
A1  - Nieberler, Matthias
A1  - Grotmeyer, Alexander
A1  - Maiellaro, Isabella
A1  - Gao, Shiqiang
A1  - Beck, Sebastian
A1  - Pawlak, Matthias
A1  - Sauer, Markus
A1  - Asan, Esther
A1  - Rothemund, Sven
A1  - Winkler, Jana
A1  - Prömel, Simone
A1  - Nagel, Georg
A1  - Langenhan, Tobias
A1  - Kittel, Robert J
T1  - Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons
JF  - eLife
N2  - Adhesion-type G protein-coupled receptors (aGPCRs), a large molecule family with over 30 members in humans, operate in organ development, brain function and govern immunological responses. Correspondingly, this receptor family is linked to a multitude of diverse human diseases. aGPCRs have been suggested to possess mechanosensory properties, though their mechanism of action is fully unknown. Here we show that the Drosophila aGPCR Latrophilin/dCIRL acts in mechanosensory neurons by modulating ionotropic receptor currents, the initiating step of cellular mechanosensation. This process depends on the length of the extended ectodomain and the tethered agonist of the receptor, but not on its autoproteolysis, a characteristic biochemical feature of the aGPCR family. Intracellularly, dCIRL quenches cAMP levels upon mechanical activation thereby specifically increasing the mechanosensitivity of neurons. These results provide direct evidence that the aGPCR dCIRL acts as a molecular sensor and signal transducer that detects and converts mechanical stimuli into a metabotropic response.
KW  - Latrophilin
KW  - adhesion GPCR
KW  - dCIRL
KW  - sensory physiology
KW  - metabotropic signalling
KW  - mechanotransduction
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170520
VL  - 6
IS  - e28360
ER  -