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. 2014 Sep 18;8:327. doi: 10.3389/fnbeh.2014.00327

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Copyright © 2014 Peña, Childs, Willett, Vital, McIntyre, and Kroener.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Vagus nerve stimulation enhances extinction of auditory fear conditioning. (A) Experimental timeline. Auditory fear conditioning consisted of 2 days of training with eight pairings between a tone (CS) and a footshock (UCS) per day. On Day 3 rats were exposed four times to the conditioned tone in the absence of footshock and freezing levels were tested (Conditioned Fear Test). On Day 4 (Treatment) rats received group-specific treatment: four tone presentations were paired with either VNS or sham-stimulation. Rats in the extended-extinction group received 20 tone presentations. Freezing levels were tested again on Day 5 in response to four presentations of the CS alone (Post Treatment test). (B) Percentage of time spent freezing during presentation of the conditioned stimulus (CS) on Day 3 (D3, white bars) and Day 5 (D5), respectively, for the different treatment groups (4 tones + sham stimulation, four tones + VNS, and extended extinction, EE, with 20 tones + sham stimulation). Presentation of the Day 3 and Day 5 freezing responses is separated into groups of rats in which subsequently the plasticity of the IL-BLA pathway was tested with either high-frequency (HFS) or low-frequency stimulation (LFS) of the IL. After 1 day of extinction training paired with VNS (black bar) rats spent significantly less time freezing than sham controls (^* p < 0.05). Similar levels of fear extinction were observed when rats were given extended extinction (gray bar). (C) Percentage of time spent freezing during the inter-tone intervals (ITI) on Day 3 (D3, white bars) and Day 5 (D5), respectively, for the same groups shown in (B). Freezing levels during ITI might serve as a measure of whether extinction training generalizes to the context. Animals receiving extended extinction training did not differ significantly in their behavior from sham stimulated animals during ITIs; however, VNS animals also showed reduced freezing behavior outside the presentation of the conditioned tone.