Cellular and molecular mechanisms of synaptic specificity

Annu Rev Cell Dev Biol. 2014;30:417-37. doi: 10.1146/annurev-cellbio-100913-012953. Epub 2014 Aug 15.


Precise connectivity in neuronal circuits is a prerequisite for proper brain function. The dauntingly complex environment encountered by axons and dendrites, even after navigation to their target area, prompts the question of how specificity of synaptic connections arises during development. We review developmental strategies and molecular mechanisms that are used by neurons to ensure their precise matching of pre- and postsynaptic elements. The emerging theme is that each circuit uses a combination of simple mechanisms to achieve its refined, often complex connectivity pattern. At increasing levels of resolution, from lamina choice to subcellular targeting, similar signaling concepts are reemployed to narrow the choice of potential matches. Temporal control over synapse development and synapse elimination further ensures the specificity of connections in the nervous system.

Keywords: neuronal circuits; neuronal development; signaling; synapse development.

Publication types

  • Review

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / physiology
  • Cell Adhesion
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Drosophila melanogaster / physiology
  • Eye Proteins / metabolism
  • Growth Cones / physiology
  • Humans
  • Membrane Proteins / metabolism
  • Neurons / physiology
  • Neurons / ultrastructure
  • Photoreceptor Cells, Invertebrate / physiology
  • Photoreceptor Cells, Invertebrate / ultrastructure
  • Retina / cytology
  • Synapses / physiology*
  • Synaptic Transmission
  • Time Factors


  • Cell Adhesion Molecules, Neuronal
  • Eye Proteins
  • Membrane Proteins