title: A distinct entorhinal cortex to hippocampal CA1 direct circuit for olfactory associative learning.
abstract: Lateral and medial parts of entorhinal cortex (EC) convey nonspatial 'what' and spatial 'where' information, respectively, into hippocampal CA1, via both the indirect EC layer 2→ hippocampal dentate gyrus→CA3→CA1 and the direct EC layer 3→CA1 paths. However, it remains elusive how the direct path transfers distinct information and contributes to hippocampal learning functions. Here we report that lateral EC projection neurons selectively form direct excitatory synapses onto a subpopulation of morphologically complex, calbindin-expressing pyramidal cells (PCs) in the dorsal CA1 (dCA1), while medial EC neurons uniformly innervate all dCA1 PCs. Optogenetically inactivating the distinct lateral EC-dCA1 connections or the postsynaptic dCA1 calbindin-expressing PC activity slows olfactory associative learning. Moreover, optetrode recordings reveal that dCA1 calbindin-expressing PCs develop more selective spiking responses to odor cues during learning. Thus, our results identify a direct lateral EC→dCA1 circuit that is required for olfactory associative learning.
authors.affiliation: Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|State Key Laboratory of Cognitive Neuroscience &Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.|University of Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yiding
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Brain Functional Genomics-Ministry of Education, School of Life Science, East China Normal University, Shanghai, China.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Britton Chance Center for Biomedical Photonics and Department of Biomedical Engineering, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|University of Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Cognitive Neuroscience &Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, CAS Center for Excellence in Brain Science and Intelligence Technology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education and State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Cognitive Neuroscience &Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
authors.forename: Malte J
authors.identifier: http://orcid.org/0000-0002-7988-4624
authors.initials: MJ
authors.lastname: Rasch
authors.affiliation: State Key Laboratory of Virology, CAS Center for Excellence in Brain Science and Intelligence Technology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Haifei
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Cognitive Neuroscience &Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Cognitive Neuroscience &Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology, CAS Center for Excellence in Brain Science and Intelligence Technology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Minhua
authors.initials: M
authors.lastname: Luo
authors.affiliation: Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education and State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, China.
authors.forename: Junlin
authors.initials: J
authors.lastname: Teng
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education and State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
authors.affiliation: Britton Chance Center for Biomedical Photonics and Department of Biomedical Engineering, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shaoqun
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Brain Functional Genomics-Ministry of Education, School of Life Science, East China Normal University, Shanghai, China.
authors.forename: Longnian
authors.initials: L
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Cognitive Neuroscience &Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D064026:Calbindins / Q000378:metabolism; D018728:Entorhinal Cortex / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000502:physiology; D009812:Odorants; D055696:Olfactory Perception / Q000502:physiology*; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology
chemical_list: D064026:Calbindins