title: Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations.
abstract: Targeting genetically encoded tools for neural circuit dissection to relevant cellular populations is a major challenge in neurobiology. We developed an approach, targeted recombination in active populations (TRAP), to obtain genetic access to neurons that were activated by defined stimuli. This method utilizes mice in which the tamoxifen-dependent recombinase CreER(T2) is expressed in an activity-dependent manner from the loci of the immediate early genes Arc and Fos. Active cells that express CreER(T2) can only undergo recombination when tamoxifen is present, allowing genetic access to neurons that are active during a time window of less than 12 hr. We show that TRAP can provide selective access to neurons activated by specific somatosensory, visual, and auditory stimuli and by experience in a novel environment. When combined with tools for labeling, tracing, recording, and manipulating neurons, TRAP offers a powerful approach for understanding how the brain processes information and generates behavior.
authors.affiliation: Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
authors.forename: Casey J
authors.initials: CJ
authors.lastname: Guenthner
authors.forename: Kazunari
authors.initials: K
authors.lastname: Miyamichi
authors.forename: Helen H
authors.initials: HH
authors.lastname: Yang
authors.forename: H Craig
authors.initials: HC
authors.lastname: Heller
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002452:Cell Count; D002540:Cerebral Cortex / Q000166:cytology*; D003598:Cytoskeletal Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology; D006915:Hydroxytestosterones / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D016761:Oncogene Proteins v-fos / Q000235:genetics; D010775:Photic Stimulation; D012333:RNA, Messenger / Q000378:metabolism; D045522:Recombinases / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics*; D012683:Sensory Deprivation; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors; D014738:Vibrissae / Q000294:innervation
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003598:Cytoskeletal Proteins; D006915:Hydroxytestosterones; D009419:Nerve Tissue Proteins; D016761:Oncogene Proteins v-fos; D012333:RNA, Messenger; D045522:Recombinases; C092069:activity regulated cytoskeletal-associated protein; D013629:Tamoxifen; C032278:4,17 beta-dihydroxy-4-androstene-3-one