{"doi":"10.1126/scitranslmed.add1014","title":"Expression of the excitatory opsin ChRERα can be traced longitudinally in rat and nonhuman primate brains with PET imaging","abstract":"Optogenetics is a widely used technology with potential for translational research. A critical component of such applications is the ability to track the location of the transduced opsin in vivo. To address this problem, we engineered an excitatory opsin, ChRERα (hChR2(134R)-V5-ERα-LBD), that could be visualized using positron emission tomography (PET) imaging in a noninvasive, longitudinal, and quantitative manner. ChRERα consists of the prototypical excitatory opsin channelrhodopsin-2 (ChR2) and the ligand-binding domain (LBD) of the human estrogen receptor α (ERα). ChRERα showed conserved ChR2 functionality and high affinity for [ 18 F]16α-fluoroestradiol (FES), an FDA-approved PET radiopharmaceutical. Experiments in rats demonstrated that adeno-associated virus (AAV)–mediated expression of ChRERα enables neural circuit manipulation in vivo and that ChRERα expression could be monitored using FES-PET imaging. In vivo experiments in nonhuman primates (NHPs) confirmed that ChRERα expression could be monitored at the site of AAV injection in the primary motor cortex and in long-range neuronal terminals for up to 80 weeks. The anatomical connectivity map of the primary motor cortex identified by FES-PET imaging of ChRERα expression overlapped with a functional connectivity map identified using resting state fMRI in a separate cohort of NHPs. Overall, our results demonstrate that ChRERα expression can be mapped longitudinally in the mammalian brain using FES-PET imaging and can be used for neural circuit modulation in vivo.","journal":"Science Translational Medicine","year":2023,"id":351461,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":449149,"name":"Matthew A. Boehm","orcid":"0000-0002-9977-270X","position":1,"is_corresponding":false},{"id":268782,"name":"Hank P. Jedema","orcid":"0000-0002-7869-2110","position":2,"is_corresponding":false},{"id":620552,"name":"Óscar Solís","orcid":"0000-0002-8285-5891","position":3,"is_corresponding":false},{"id":314824,"name":"Marco Pignatelli","orcid":"0000-0002-8437-3343","position":4,"is_corresponding":false},{"id":474512,"name":"Xiaowei Song","orcid":"0000-0001-9694-6594","position":5,"is_corresponding":false},{"id":293598,"name":"Hanbing Lu","orcid":null,"position":6,"is_corresponding":false},{"id":481502,"name":"Christopher T. Richie","orcid":"0000-0002-7944-4928","position":7,"is_corresponding":false},{"id":865761,"name":"Shiliang Zhang","orcid":"0000-0001-8414-6178","position":8,"is_corresponding":false},{"id":620551,"name":"Juan L. Gomez","orcid":"0000-0003-3170-9904","position":9,"is_corresponding":false},{"id":450195,"name":"Sherry Lam","orcid":null,"position":10,"is_corresponding":false},{"id":262801,"name":"Marisela Morales","orcid":"0000-0002-3845-9402","position":11,"is_corresponding":false},{"id":473491,"name":"Omar A. Gharbawie","orcid":"0000-0002-2744-9305","position":12,"is_corresponding":false},{"id":7932,"name":"Martin G. Pomper","orcid":"0000-0001-6753-3010","position":13,"is_corresponding":false},{"id":291969,"name":"Elliot A. Stein","orcid":"0000-0003-0593-0269","position":14,"is_corresponding":false},{"id":474513,"name":"Charles W. Bradberry","orcid":"0000-0003-2630-4144","position":15,"is_corresponding":false},{"id":620553,"name":"Michael Michaelides","orcid":"0000-0003-0398-4917","position":16,"is_corresponding":false},{"id":449147,"name":"Jordi Bonaventura","orcid":"0000-0002-4745-0151","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T01:12:41.740237Z","pmid":"37494470","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}