title: NCS-1 in the dentate gyrus promotes exploration, synaptic plasticity, and rapid acquisition of spatial memory.
abstract: The molecular underpinnings of exploration and its link to learning and memory remain poorly understood. Here we show that inducible, modest overexpression of neuronal calcium sensor 1 (Ncs1) selectively in the adult murine dentate gyrus (DG) promotes a specific form of exploratory behavior. The mice also display a selective facilitation of long-term potentiation (LTP) in the medial perforant path and a selective enhancement in rapid-acquisition spatial memory, phenotypes that are reversed by direct application of a cell-permeant peptide (DNIP) designed to interfere with NCS-1 binding to the dopamine type-2 receptor (D2R). Moreover, the DNIP and the D2R-selective antagonist L-741,626 attenuated exploratory behavior, DG LTP, and spatial memory in control mice. These data demonstrate a role for NCS-1 and D2R in DG plasticity and provide insight for understanding how the DG contributes to the origin of exploration and spatial memory acquisition.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada. saab@lunenfeld.ca
authors.forename: Bechara J
authors.initials: BJ
authors.lastname: Saab
authors.forename: John
authors.initials: J
authors.lastname: Georgiou
authors.forename: Arup
authors.initials: A
authors.lastname: Nath
authors.forename: Frank J S
authors.initials: FJ
authors.lastname: Lee
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Aubin
authors.initials: A
authors.lastname: Michalon
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Mansuy
authors.forename: John C
authors.initials: JC
authors.lastname: Roder
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007858:Learning / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051580:Neuronal Calcium-Sensor Proteins / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D009483:Neuropsychological Tests; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007211:Indoles; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D010880:Piperidines; D017448:Receptors, Dopamine D2; C101464:frequenin calcium sensor proteins; C104750:3-(4-(4-chlorophenyl-4-hydroxypiperidino)methyl)indole