An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development
Xinglong Gu1, Liang Zhou1, Wei Lu1
1Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 3C1000, Bethesda, MD 20892, USA.
Cell Reports
|January 18, 2016
Summary
NMDA-type ionotropic glutamate receptors (NMDARs) are essential for developing inhibitory GABAergic synapses in the mammalian brain. Their absence reduces synaptic transmission but increases tonic inhibition, revealing a compensatory mechanism.
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Developmental Biology
Background:
- GABAergic synaptic transmission balances excitatory drive in the mammalian brain.
- Molecular mechanisms of GABAergic synapse development are not fully understood.
Purpose of the Study:
- To investigate the role of NMDA-type ionotropic glutamate receptors (NMDARs) in the development of GABAergic synapses.
- To elucidate the molecular signaling pathways involved in NMDAR-mediated GABAergic synapse development.
Main Methods:
- Studied immature neurons.
- Investigated signaling via the Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit.
- Analyzed GABAergic synaptic transmission and tonic inhibition in neurons lacking NMDARs.
Main Results:
- NMDARs are essential upstream signaling molecules for GABAergic synapse development.
- Signaling via the NMDAR GluN1 subunit's C0 domain Calmodulin binding motif is required.
- Neurons lacking NMDARs exhibit reduced GABAergic synaptic transmission.
- Tonic inhibition mediated by extrasynaptic GABAA receptors is increased in NMDAR-deficient neurons.
Conclusions:
- NMDARs play a crucial role in specifying inhibitory synapse development.
- A compensatory mechanism increases tonic inhibition when synaptic inhibition is reduced.
- NMDARs are key to establishing the balance between excitation and inhibition in the developing brain.
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