title: Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits.
abstract: The formation and recall of episodic memory requires precise information processing by the entorhinal-hippocampal network. For several decades, the trisynaptic circuit entorhinal cortex layer II (ECII)→dentate gyrus→CA3→CA1 and the monosynaptic circuit ECIII→CA1 have been considered the primary substrates of the network responsible for learning and memory. Circuits linked to another hippocampal region, CA2, have only recently come to light. Using highly cell type-specific transgenic mouse lines, optogenetics and patch-clamp recordings, we found that dentate gyrus cells, long believed to not project to CA2, send functional monosynaptic inputs to CA2 pyramidal cells through abundant longitudinal projections. CA2 innervated CA1 to complete an alternate trisynaptic circuit, but, unlike CA3, projected preferentially to the deep, rather than to the superficial, sublayer of CA1. Furthermore, contrary to existing knowledge, ECIII did not project to CA2. Our results allow a deeper understanding of the biology of learning and memory.
authors: RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. keigo@mit.edu
authors: Keigo
authors: K
authors: Kohara
authors: RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Michele
authors: M
authors: Pignatelli
authors: RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Alexander J
authors: AJ
authors: Rivest
authors: RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Hae-Yoon
authors: HY
authors: Jung
authors: RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Takashi
authors: T
authors: Kitamura
authors: RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Junghyup
authors: J
authors: Suh
authors: RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Dominic
authors: D
authors: Frank
authors: RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Koichiro
authors: K
authors: Kajikawa
authors: RIKEN BioResource Center, Tsukuba, Ibaraki, Japan;  Department of Environmental Preventive Medicine, Jichi Medical University, Tochigi, Japan.
authors: Nathan
authors: N
authors: Mise
authors: RIKEN BioResource Center, Tsukuba, Ibaraki, Japan.
authors: Yuichi
authors: Y
authors: Obata
authors: Genetic Neuroengineering Group, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Ian R
authors: IR
authors: Wickersham
authors: RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. tonegawa@mit.edu
authors: Susumu
authors: S
authors: Tonegawa
mesh_terms: D000818:Animals; D056651:CA2 Region, Hippocampal / Q000166:cytology*; D018728:Entorhinal Cortex / Q000166:cytology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009412:Nerve Fibers / Q000502:physiology; D009415:Nerve Net / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008164:Luminescent Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020710:RGS Proteins; C488188:Rgs1 protein, mouse