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. 2018 Aug 6;8:11740. doi: 10.1038/s41598-018-29979-2

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Patterns of neuronal response to GO/NoGO cues in the PFC and VTA. (a) Summary of the GO/NoGO paradigm used. A random 1–3 s pre-stimulus delay was followed by a 1 s tone (1 KHz or 8 KHz), after which the licking response was measured during a 2 s opportunity window. Only correct GO responses were rewarded with a drop of water, while correct NoGO trials were followed by a shorter inter-trial interval (ITI), giving the chance to get water sooner in subsequent trials. Four out of six trained animals achieved the criterion of session performance higher than 80% (dashed line) with a NoGO performance higher than 60%. (b) Left: recording sites for all PFC - VTA electrode placements relative from bregma. Each dot represents the electrode position for a specific recording session. Right: Raster plots illustrating examples of licking responses (in black) and spiking activity of a PFC neuron and a VTA neuron during 30 consecutive correct GO trials (blue) and NoGO trials (red). Note the increment in firing rate immediately after presentation of the tone. (c) Relative to baseline values (mean +/− s.e.m., 100 ms bins), PFC and VTA neurons increased their mean firing rate (%ΔFR) following the presentation of GO and NoGO cues. However, this increment was significantly greater during GO trials in both PFC (n = 95, p < 0.01, GO vs. NoGO, Sign test) and pDA (n = 94, p < 0.0001, GO vs. NoGO, Sign test) neurons. In contrast, Non-DA cells exhibited similar patterns of response during GO and NoGO trials (n = 59, p = 0.6, GO vs. NoGO, Sign test). (d) Granger-causality analysis of the mean firing rate revealed an asymmetric directionality from the VTA to the PFC. Only the GCI for the pDA group is statistically different from the expected GCI under the hypothesis of no temporal structure. This suggests that pDA neurons (not Non-DA neurons) are likely to Granger-cause PFC cell firing during tone presentation. The numbers next to the arrows indicate the n of pairs of PFC-VTA neurons for each interaction. (e) Dot plot showing PFC, pDA and Non-DA neuronal responses (ΔFR relatively to baseline) during GO and NoGO trials. In blue are neurons exhibiting higher firing rate during GO trials whereas in red are neurons responding with higher firing rate during NoGO trials. (f) Examples of peri-stimulus time histograms (10 ms bins) illustrating the pattern of neuronal responses from the GO > NoGO (top) and the NoGO > GO (bottom) groups. Scale bar: 1 ms.