title: Reward-timing-dependent bidirectional modulation of cortical microcircuits during optical single-neuron operant conditioning.
abstract: Animals rapidly adapt to environmental change. To reveal how cortical microcircuits are rapidly reorganized when an animal recognizes novel reward contingency, we conduct two-photon calcium imaging of layer 2/3 motor cortex neurons in mice and simultaneously reinforce the activity of a single cortical neuron with water delivery. Here we show that when the target neuron is not relevant to a pre-trained forelimb movement, the mouse increases the target neuron activity and the number of rewards delivered during 15-min operant conditioning without changing forelimb movement behaviour. The reinforcement bidirectionally modulates the activity of subsets of non-target neurons, independent of distance from the target neuron. The bidirectional modulation depends on the relative timing between the reward delivery and the neuronal activity, and is recreated by pairing reward delivery and photoactivation of a subset of neurons. Reward-timing-dependent bidirectional modulation may be one of the fundamental processes in microcircuit reorganization for rapid adaptation.
authors.affiliation: 1] Division of Brain Circuits, National Institute for Basic Biology and the Graduate University of Advanced Studies (Sokendai), Myodaiji, Okazaki, Japan [2] Japan Science and Technology Agency, CREST, Saitama 332-0012, Japan.
authors.forename: Riichiro
authors.initials: R
authors.lastname: Hira
authors.affiliation: 1] Division of Brain Circuits, National Institute for Basic Biology and the Graduate University of Advanced Studies (Sokendai), Myodaiji, Okazaki, Japan [2] Japan Science and Technology Agency, CREST, Saitama 332-0012, Japan.
authors.forename: Fuki
authors.initials: F
authors.lastname: Ohkubo
authors.affiliation: 1] Division of Brain Circuits, National Institute for Basic Biology and the Graduate University of Advanced Studies (Sokendai), Myodaiji, Okazaki, Japan [2] Japan Science and Technology Agency, CREST, Saitama 332-0012, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Masamizu
authors.affiliation: Brain Science Institute, Saitama University, Saitama 338-8570, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ohkura
authors.affiliation: Brain Science Institute, Saitama University, Saitama 338-8570, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Nakai
authors.affiliation: Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okada
authors.affiliation: 1] Division of Brain Circuits, National Institute for Basic Biology and the Graduate University of Advanced Studies (Sokendai), Myodaiji, Okazaki, Japan [2] Japan Science and Technology Agency, CREST, Saitama 332-0012, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsuzaki
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000222:Adaptation, Physiological; D000818:Animals; D058256:Brain Waves / Q000502:physiology; D003216:Conditioning, Operant / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009044:Motor Cortex / Q000166:cytology / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology*; D012054:Reinforcement, Psychology; D012201:Reward