NMDA receptors in GABAergic synapses during postnatal development.
Csaba Cserép1, Eszter Szabadits, András Szőnyi
1Laboratory of Cerebral Cortex Research, Department of Cellular and Network Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
Plos One
|June 5, 2012
Summary
During early brain development, gamma-aminobutyric-acid (GABA) and N-methyl-D-aspartate receptors (NMDARs) cooperate within GABAergic synapses to support neuronal network formation. This study reveals NMDARs are postsynaptically located at both GABAergic and glutamatergic synapses.
Area of Science:
- Neuroscience
- Developmental Biology
- Synaptic Plasticity
Background:
- Gamma-aminobutyric-acid (GABA) is the primary inhibitory neurotransmitter in adult brains but acts depolarizingly during development.
- This developmental GABAergic depolarization is crucial for spontaneous synchronous activity (SSA) and neuronal network formation, cooperating with N-methyl-D-aspartate receptors (NMDARs).
- The precise subcellular localization of NMDARs relative to GABAergic synapses during this critical developmental period remains largely unknown.
Purpose of the Study:
- To investigate the subcellular distribution of NMDARs in association with GABAergic synapses in the developing mouse hippocampus.
- To elucidate the anatomical basis for the functional cooperation between GABAergic depolarization and NMDAR activation during early neuronal development.
Main Methods:
- Utilized multiple immunofluorescent labeling and confocal laser-scanning microscopy in postnatal day 6-7 mouse hippocampus.
- Employed electron microscopy with pre-embedding immunogold-immunoperoxidase reactions to confirm receptor localization.
- Conducted quantitative post-embedding immunogold labeling to determine receptor densities at different synaptic locations.
Main Results:
- NMDARs were found to be associated with both glutamatergic and GABAergic synapses, with direct colocalization of GABA(A) and NMDAR labeling observed at GABAergic synapses.
- Electron microscopy confirmed postsynaptic expression of GluN1, GluN2A, and GluN2B NMDAR subunits at both synapse types.
- NMDAR density was significantly higher at glutamatergic synapses compared to GABAergic synapses, though total receptor numbers were similar due to larger GABAergic synapse size. Synaptic receptor density exceeded extrasynaptic levels.
Conclusions:
- NMDARs are postsynaptically localized at GABAergic synapses, providing a neuroanatomical basis for the functional cooperation between GABA(A) receptor-mediated depolarization and NMDAR activation.
- This synaptic GABAergic depolarization may facilitate NMDAR activation within GABAergic synapses, enhancing the probability and efficiency of activating distal glutamatergic synapses.
- The presence of NMDARs within GABAergic synapses suggests a mechanism for activity-dependent modification of GABAergic synapses through NMDA receptor-mediated calcium influx.
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