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Cited by 698Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersCell Adhesion Molecules Research

Towards an Understanding of Synapse Formation

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Südhof, Thomas C.·2018·Neuron
DOI 10.1016/j.neuron.2018.09.040PMC PMC6226307
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Abstract

Synapses are intercellular junctions specialized for fast, point-to-point information transfer from a presynaptic neuron to a postsynaptic cell. At a synapse, a presynaptic terminal secretes neurotransmitters via a canonical release machinery, while a postsynaptic specialization senses neurotransmitters via diverse receptors. Synaptic junctions are likely organized by trans-synaptic cell-adhesion molecules (CAMs) that bidirectionally orchestrate synapse formation, restructuring, and elimination. Many candidate synaptic CAMs were described, but which CAMs are central actors and which are bystanders remains unclear. Moreover, multiple genes encoding synaptic CAMs were linked to neuropsychiatric disorders, but the mechanisms involved are unresolved. Here, I propose that engagement of multifarious synaptic CAMs produces parallel trans-synaptic signals that mediate the establishment, organization, and plasticity of synapses, thereby controlling information processing by neural circuits. Among others, this hypothesis implies that synapse formation can be understood in terms of inter- and intracellular signaling, and that neuropsychiatric disorders involve an impairment in such signaling.

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  • The unique properties of individual synapses are regulated through a continuous interplay of bidirectional signals exchanged between the presynaptic and postsynaptic compartments.

    “The unique properties of individual synapses are regulated through a continuous interplay of bidirectional signals exchanged between the presynaptic and postsynaptic compartments [3,4].”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [3]

  • The complex architecture of a synapse, characterized by its asymmetric organization, enables unidirectional signal propagation from the presynaptic terminal to the postsynaptic neuron.

    “The complex architecture of a synapse, characterized by its asymmetric organization, enables unidirectional signal propagation from the presynaptic terminal to the postsynaptic neuron [2,3,4].”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [3]

  • The formation, maturation, and selective elimination of synapses are dynamic processes essential for the precise wiring of neural circuits during development and for maintaining brain function throughout life.

    “The formation, maturation, and selective elimination of synapses are dynamic processes essential for the precise wiring of neural circuits during development and for maintaining brain function throughout life [1,3].”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [3]

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Authors
Südhof, T. C.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Südhof, Thomas C.
ORCID
Südhof, Thomas C.
Venue
Neuron
Publisher
Elsevier BV
Published
2018-10
Volume
100
Issue
2
Pages
276-293
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2018.09.040
PMC
PMC6226307
OpenAlex
W2898460257
Cited by
698
References
148
Citations by year
2026: 87 · 2025: 104 · 2024: 105 · 2023: 79 · 2022: 80 · 2021: 99 · 2020: 102 · 2019: 41
FWCI
7.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH (MH052804, MH104172, AG048131, MH086403, MH092931, Howard Hughes Medical Institute)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
synaptogenesis, synapses, presynaptic terminals, postsynaptic receptors, neurotransmitter release, synaptic pruning, synaptic plasticity, neuropsychiatric disorders, intercellular communication, neural circuits
MeSH terms
Animals, Brain, Humans, Neuronal Plasticity, Synapses, Signal Transduction, Cell Adhesion Molecules, Neurogenesis

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