PMID- 33446857 OWN - NLM STAT- MEDLINE DCOM- 20210709 LR - 20240226 IS - 2399-3642 (Electronic) IS - 2399-3642 (Linking) VI - 4 IP - 1 DP - 2021 Jan 14 TI - Whole brain dynamics during optogenetic self-stimulation of the medial prefrontal cortex in mice. PG - 66 LID - 10.1038/s42003-020-01612-x [doi] LID - 66 AB - Intracranial self-stimulation, in which an animal performs an operant response to receive regional brain electrical stimulation, is a widely used procedure to study motivated behavior. While local neuronal activity has long been measured immediately before or after the operant, imaging the whole brain in real-time remains a challenge. Herein we report a method that permits functional MRI (fMRI) of brain dynamics while mice are cued to perform an operant task: licking a spout to receive optogenetic stimulation to the medial prefrontal cortex (MPFC) during a cue ON, but not cue OFF. Licking during cue ON results in activation of a widely distributed network consistent with underlying MPFC projections, while licking during cue OFF (without optogenetic stimulation) leads to negative fMRI signal in brain regions involved in acute extinction. Noninvasive whole brain readout combined with circuit-specific neuromodulation opens an avenue for investigating adaptive behavior in both healthy and disease models. FAU - Cover, Christopher G AU - Cover CG AD - Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD, 21224, USA. FAU - Kesner, Andrew J AU - Kesner AJ AD - Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD, 21224, USA. FAU - Ukani, Shehzad AU - Ukani S AD - Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD, 21224, USA. FAU - Stein, Elliot A AU - Stein EA AUID- ORCID: 0000-0003-0593-0269 AD - Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD, 21224, USA. FAU - Ikemoto, Satoshi AU - Ikemoto S AUID- ORCID: 0000-0002-0732-7386 AD - Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD, 21224, USA. FAU - Yang, Yihong AU - Yang Y AD - Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD, 21224, USA. yihongyang@mail.nih.gov. FAU - Lu, Hanbing AU - Lu H AUID- ORCID: 0000-0003-0469-4321 AD - Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD, 21224, USA. luha@mail.nih.gov. LA - eng PT - Journal Article PT - Research Support, N.I.H., Intramural DEP - 20210114 PL - England TA - Commun Biol JT - Communications biology JID - 101719179 RN - 57-50-1 (Sucrose) SB - IM MH - Animals MH - Behavior, Animal/physiology MH - Brain/*diagnostic imaging/*physiology MH - Cues MH - Magnetic Resonance Imaging MH - Male MH - Mice, Inbred C57BL MH - Optogenetics/*methods MH - Prefrontal Cortex/physiology MH - Sucrose MH - Mice PMC - PMC7809041 COIS- H.L., Y.Y. and E.A.S. are the inventors of a patent (US9717946B2) issued to the National Institutes of Health in 2017. The behavioral training method and imaging platform were disclosed in the patent. The remaining authors declare no competing interests. EDAT- 2021/01/16 06:00 MHDA- 2021/07/10 06:00 PMCR- 2021/01/14 CRDT- 2021/01/15 05:57 PHST- 2020/03/12 00:00 [received] PHST- 2020/12/01 00:00 [accepted] PHST- 2021/01/15 05:57 [entrez] PHST- 2021/01/16 06:00 [pubmed] PHST- 2021/07/10 06:00 [medline] PHST- 2021/01/14 00:00 [pmc-release] AID - 10.1038/s42003-020-01612-x [pii] AID - 1612 [pii] AID - 10.1038/s42003-020-01612-x [doi] PST - epublish SO - Commun Biol. 2021 Jan 14;4(1):66. doi: 10.1038/s42003-020-01612-x.