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. 2022 Mar 16;13:1386. doi: 10.1038/s41467-022-28892-7

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© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022

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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Fig. 3 — a Each rat received AAV-ChR2-EYFP or AAV-EYFP injected into the IL followed by the implantation of an optic fiber at the same region. b ICSS: The rats (n = 7) received photostimulation (a train of 8 pulses at 25 Hz) upon lever pressing. After a stable response over a few sessions, the effects of the reinforcement interval (0, 1, 2, and 4 s) were evaluated with a within-subjects design in that order. Each interval was tested in a 10-min block. Data are mean lever-presses (±SEM). *P = 0.0319, **P = 0.0135, significantly lower than the continuous-reinforcement schedule (0 s) value (Tukey HSD post hoc test). c fMRI: Photostimulation (a train of 8 pulses at 25 Hz) delivered at the IL with one of three intervals (1, 2, or 4 s) during the 20-s ON phase of a 60-s block. Each block was repeated 5 times for each train interval. Effects of reinforcement intervals were determined in both descending- and ascending-order sessions. The vertical axis indicates raw BOLD signal intensity of one mPFC voxel in arbitrary unit. d The unilateral photostimulation with the 1-s interval activated the entire medial network of the PFC, including the medial orbital, prelimbic, ventral anterior cingulate, and infralimbic regions, with stimulation-side dominance. It also elicited significant BOLD signals in extensive subcortical regions of the mPFC (top; n = 10), but limited signals in the control group (middle; n = 7). Significant differences in BOLD signal between the ChR2 and control groups are shown in the bottom panel. Imaging results were corrected for whole-brain multiple comparisons (Corrected P < 0.05). AI anterior insular region, Amyg amygdala, ATh anterior thalamic area, BST bed nucleus of stria terminalis, MD mediodorsal region, POA preoptic area, VP ventral pallidum, VStr ventral striatum. e Significant correlations (Pearson’s r) between ICSS responses and the levels of BOLD signals in the AI, VStr, ATh, and hypothalamus. Each dot represents the data of a single rat.