NCS-1 in the dentate gyrus promotes exploration, synaptic plasticity, and rapid acquisition of spatial memory

Bechara J Saab; John Georgiou; Arup Nath; Frank J S Lee; Min Wang; Aubin Michalon; Fang Liu; Isabelle M Mansuy; John C Roder

doi:10.1016/j.neuron.2009.08.014

NCS-1 in the dentate gyrus promotes exploration, synaptic plasticity, and rapid acquisition of spatial memory

Neuron. 2009 Sep 10;63(5):643-56. doi: 10.1016/j.neuron.2009.08.014.

Authors

Bechara J Saab¹, John Georgiou, Arup Nath, Frank J S Lee, Min Wang, Aubin Michalon, Fang Liu, Isabelle M Mansuy, John C Roder

Affiliation

¹ Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada. saab@lunenfeld.ca

PMID: 19755107
DOI: 10.1016/j.neuron.2009.08.014

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
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
Learning / drug effects
Learning / physiology
Long-Term Potentiation / drug effects
Long-Term Potentiation / physiology*
Maze Learning / drug effects
Maze Learning / physiology
Memory / drug effects
Memory / physiology*
Mice
Mice, Transgenic
Models, Neurological
Motor Activity / drug effects
Motor Activity / physiology
Neuronal Calcium-Sensor Proteins / metabolism*
Neuropeptides / metabolism*
Neuropsychological Tests
Piperidines / pharmacology
Rats
Receptors, Dopamine D2 / metabolism
Recognition, Psychology / drug effects
Recognition, Psychology / physiology
Space Perception / drug effects
Space Perception / physiology*
Time Factors

Substances

Dopamine Antagonists
Dopamine D2 Receptor Antagonists
Indoles
Neuronal Calcium-Sensor Proteins
Neuropeptides
Piperidines
Receptors, Dopamine D2
frequenin calcium sensor proteins
3-(4-(4-chlorophenyl-4-hydroxypiperidino)methyl)indole