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.

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