NCS-1 in the Dentate Gyrus Promotes Exploration, Synaptic Plasticity, and Rapid Acquisition of Spatial Memory

• Published in: Neuron (Cambridge, Mass.) Vol. 63; no. 5; pp. 643 - 656
• Main Authors: Saab, Bechara J., Georgiou, John, Nath, Arup, Lee, Frank J.S., Wang, Min, Michalon, Aubin, Liu, Fang, Mansuy, Isabelle M., Roder, John C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10-09-2009; Elsevier Limited
• Subjects: Acquisitions & mergers; Animal memory; Animals; Behavior; Cell Membrane - metabolism; Dentate Gyrus - drug effects; Dentate Gyrus - physiology; Dopamine Antagonists - pharmacology; Dopamine D2 Receptor Antagonists; Exploratory Behavior - drug effects; Exploratory Behavior - physiology; In Vitro Techniques; Indoles - pharmacology; Kinases; Learning - drug effects; Learning - physiology; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Mammals; Maze Learning - drug effects; Maze Learning - physiology; Memory - drug effects; Memory - physiology; Mice; Mice, Transgenic; Models, Neurological; MOLNEURO; Motor Activity - drug effects; Motor Activity - physiology; Neuronal Calcium-Sensor Proteins - metabolism; Neurons; Neuropeptides - metabolism; Neuropsychological Tests; Peptides; Piperidines - pharmacology; PROTEINS; Rats; Receptors, Dopamine D2 - metabolism; Recognition (Psychology) - drug effects; Recognition (Psychology) - physiology; Rodents; Space Perception - drug effects; Space Perception - physiology; SYSNEURO; Time Factors; SYSNEURO; PROTEINS; MOLNEURO
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2009.08.014

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.