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Some assembly required: the development of neuronal synapses

Nature Reviews Molecular Cell Biology volume 4, pages 833–841 (2003)Cite this article

Key Points

  • During brain development, central excitatory synapses increase in number and change in morphology.

  • Specific cell-surface molecules are believed to mediate dendrite–axon contact and to have a role in synapse formation and/or maturation.

  • The time course for the molecular assembly of the synapse has been studied in neuronal cultures and occurs rapidly (∼1 hour).

  • Functional maturation and morphological growth of synapses occurs on both the presynaptic and postsynaptic sides — for example, enhanced neurotransmitter release, the enlargement of dendritic spines and the recruitment of postsynaptic AMPA receptors.

  • Synaptic activity seems not to be required for synapse formation per se.

  • Many questions regarding synapse development remain unanswered, including the underlying signalling pathways, the molecular basis of synapse specificity and the mechanisms of synapse elimination.

Abstract

Neurons in the brain touch and communicate with each other at specialized contacts called synapses. So, how do these tiny intercellular junctions form during development? The assembly of neuronal synapses proceeds through several stages, and occurs with surprising speed. Recent biochemical, genetic and imaging studies are beginning to disclose the molecular mechanisms that underlie synapse formation, growth and maturation.

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Figure 1: Schematic diagram of a mature excitatory synapse.
Figure 2: Trans-synaptic protein interactions that have been implicated in synaptic contact/adhesion and synapse development.
Figure 3: The sequence of molecular and morphological events in synapse assembly and maturation.

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Authors and Affiliations

  1. The Picower Center for Learning and Memory, RIKEN-Massachusetts Institute of Technology Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue (E18-215), Cambridge, 02139, Massachusetts, USA

    Zheng Li & Morgan Sheng

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  1. Zheng Li
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  2. Morgan Sheng
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DATABASES

FlyBase

Wingless

wishful thinking

Interpro

α-integrin subunit

β-integrin subunit

Swiss-Prot

α-actinin

Bassoon

CaMKII

CASK

αN-catenin

focal adhesion kinase

GluR4

β3-integrin

Munc-13

MuSK

Piccolo

SAP102

Stargazin

synaptophysin

SynCAM

talin

Wnt7a

Glossary

AXON

A thin outgrowth that typically extends a long distance from the neuronal cell body and that conveys electrical impulses to other cells that it contacts.

DENDRITE

A branching extension from the cell body that receives synaptic input from the axon of another neuron.

FILOPODIA

Thin, motile and transient actin-rich protrusions that project from the surface of cells.

GLIAL CELLS

Non-neuronal cells that provide physical and functional support for neurons, in addition to having other crucial functions in the nervous system.

PDZ DOMAIN

('PSD-95, Dlg and ZO-1'-homology domain). A conserved protein-interaction domain that is specialized for binding to specific carboxy-terminal sequences.

POSTSYNAPTIC DENSITY

(PSD). An electron-dense thickening of the postsynaptic membrane that contains a high concentration of neurotransmitter receptors, scaffolding proteins and signalling molecules.

ACTIVE ZONE

The specialized part of the presynaptic membrane, where synaptic vesicles dock and fuse with the plasma membrane and release neurotransmitter.

GABAergic SYNAPSES

Synapses that use GABA (γ-aminobutyric acid) as the neurotransmitter.

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Li, Z., Sheng, M. Some assembly required: the development of neuronal synapses. Nat Rev Mol Cell Biol 4, 833–841 (2003). https://doi.org/10.1038/nrm1242

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