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GABAergic Synaptogenesis: A Case for Cooperation
- Source :
- Neuron. 96:709-711
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- In the brain, many types of interneurons make functionally diverse inhibitory synapses onto principal neurons. While numerous molecules have been identified to function in inhibitory synapse development, it remains unknown whether there is a unifying mechanism for development of diverse inhibitory synapses. Here we report a general molecular mechanism underlying hippocampal inhibitory synapse development. In developing neurons, the establishment of GABAergic transmission depends on Neuroligin2 (NL2), a synaptic cell adhesion molecule (CAM). During maturation, inhibitory synapse development requires both NL2 and Slitrk3 (ST3), another CAM. Importantly, NL2 and ST3 interact with nanomolar affinity through their extracellular domains to synergistically promote synapse development. Selective perturbation of the NL2-ST3 interaction impairs inhibitory synapse development with consequent disruptions in hippocampal network activity and increased seizure susceptibility. Our findings reveal how unique postsynaptic CAMs work in concert to control synaptogenesis and establish a general framework for GABAergic synapse development.
- Subjects :
- 0301 basic medicine
Cell signaling
Cell Adhesion Molecules, Neuronal
Neurogenesis
Synaptogenesis
10050 Institute of Pharmacology and Toxicology
Nerve Tissue Proteins
610 Medicine & health
Cooperativity
Article
03 medical and health sciences
0302 clinical medicine
Excitatory synapse
medicine
Cell adhesion molecule
Chemistry
General Neuroscience
2800 General Neuroscience
Cell biology
030104 developmental biology
medicine.anatomical_structure
Synapses
570 Life sciences
biology
GABAergic
Neuron
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 08966273
- Volume :
- 96
- Database :
- OpenAIRE
- Journal :
- Neuron
- Accession number :
- edsair.doi.dedup.....88c396aedbf64f08cc98adff3e48b4f5