Spine-neck geometry determines NMDA receptor-dependent Ca2+ signaling in dendrites

Neuron. 2005 May 19;46(4):609-22. doi: 10.1016/j.neuron.2005.03.015.

Abstract

Increases in cytosolic Ca2+ concentration ([Ca2+]i) mediated by NMDA-sensitive glutamate receptors (NMDARs) are important for synaptic plasticity. We studied a wide variety of dendritic spines on rat CA1 pyramidal neurons in acute hippocampal slices. Two-photon uncaging and Ca2+ imaging revealed that NMDAR-mediated currents increased with spine-head volume and that even the smallest spines contained a significant number of NMDARs. The fate of Ca2+ that entered spine heads through NMDARs was governed by the shape (length and radius) of the spine neck. Larger spines had necks that permitted greater efflux of Ca2+ into the dendritic shaft, whereas smaller spines manifested a larger increase in [Ca2+]i within the spine compartment as a result of a smaller Ca2+ flux through the neck. Spine-neck geometry is thus an important determinant of spine Ca2+ signaling, allowing small spines to be the preferential sites for isolated induction of long-term potentiation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism*
  • Diagnostic Imaging / methods
  • Dose-Response Relationship, Radiation
  • Glutamates / metabolism
  • Glutamates / pharmacology
  • Hippocampus / cytology*
  • In Vitro Techniques
  • Indoles / metabolism
  • Indoles / pharmacology
  • Lasers
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Models, Neurological
  • N-Methylaspartate / pharmacology
  • Patch-Clamp Techniques / methods
  • Pyramidal Cells / cytology*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Receptors, N-Methyl-D-Aspartate / analysis
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Synaptic Transmission / radiation effects
  • Valine / analogs & derivatives*
  • Valine / pharmacology
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology

Substances

  • 4-methoxy-7-nitroindolinyl-glutamate
  • Glutamates
  • Indoles
  • Receptors, N-Methyl-D-Aspartate
  • N-Methylaspartate
  • 2-amino-5-phosphopentanoic acid
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Valine
  • Calcium