NCS-1 in the dentate gyrus promotes exploration, synaptic plasticity, and rapid acquisition of spatial memory.
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.
Saab
Bechara J
BJ
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada. saab@lunenfeld.ca
Georgiou
John
J
Nath
Arup
A
Lee
Frank J S
FJ
Wang
Min
M
Michalon
Aubin
A
Liu
Fang
F
Mansuy
Isabelle M
IM
Roder
John C
JC
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
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