Correlated Synaptic Inputs Drive Dendritic Calcium Amplification and Cooperative Plasticity during Clustered Synapse Development

Neuron. 2016 Feb 17;89(4):784-99. doi: 10.1016/j.neuron.2016.01.012. Epub 2016 Feb 4.


The mechanisms that instruct the assembly of fine-scale features of synaptic connectivity in neural circuits are only beginning to be understood. Using whole-cell electrophysiology, two-photon calcium imaging, and glutamate uncaging in hippocampal slices, we discovered a functional coupling between NMDA receptor activation and ryanodine-sensitive intracellular calcium release that dominates the spatiotemporal dynamics of activity-dependent calcium signals during synaptogenesis. This developmentally regulated calcium amplification mechanism was tuned to detect and bind spatially clustered and temporally correlated synaptic inputs and enacted a local cooperative plasticity rule between coactive neighboring synapses. Consistent with the hypothesis that synapse maturation is spatially regulated, we observed clustering of synaptic weights in developing dendritic arbors. These results reveal developmental features of NMDA receptor-dependent calcium dynamics and local plasticity rules that are suited to spatially guide synaptic connectivity patterns in emerging neural networks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Calcium / metabolism*
  • Calcium Signaling / drug effects
  • Dendrites / physiology*
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Hippocampus / cytology*
  • Hippocampus / growth & development
  • In Vitro Techniques
  • Indoles / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neuronal Plasticity / physiology*
  • Neurons / cytology*
  • Neurons / physiology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Synapses / physiology*
  • Valine / analogs & derivatives
  • Valine / pharmacology


  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Indoles
  • Quinoxalines
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • 2-amino-5-phosphopentanoic acid
  • Valine
  • Calcium
  • cyclopiazonic acid