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Inhibitory synapses in the developing auditory system are glutamatergic
Deda C Gillespie1, Gunsoo Kim, Karl Kandler
1Department of Neurobiology, University of Pittsburgh School of Medicine, W1412 Biomedical Science Tower, 3500 Terrace St., Pittsburgh, Pennsylvania 15261, USA.
Nature Neuroscience
|March 5, 2005
Summary
Immature inhibitory synapses in the rat brain release glutamate, activating NMDA receptors. This dual neurotransmitter release is key for refining inhibitory circuits during development.
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Auditory System Development
Background:
- Activity-dependent synapse refinement shapes neuronal circuits.
- Mechanisms for inhibitory circuit refinement are less understood than excitatory ones.
- Precise tonotopic maps in the mammalian sound localization system rely on inhibitory synapse refinement.
Purpose of the Study:
- Investigate the mechanisms underlying inhibitory synapse refinement in the rat lateral superior olive (LSO).
- Determine the role of neurotransmitter release from medial nucleus of the trapezoid body (MNTB) terminals in LSO circuit formation.
Main Methods:
- Immunohistochemistry to identify co-localization of neurotransmitter transporters.
- Electrophysiological recordings to assess neurotransmitter release and receptor activation.
Main Results:
- Immature inhibitory (GABA/glycinergic) synapses in the rat LSO also release glutamate.
- Vesicular glutamate transporter 3 (VGluT3) is co-localized with vesicular GABA transporter in MNTB terminals.
- Glutamatergic transmission activates postsynaptic NMDA receptors (NMDARs) at these inhibitory synapses, particularly during synapse elimination.
Conclusions:
- Single MNTB terminals release GABA, glycine, and glutamate.
- Glutamate release from inhibitory synapses plays a critical role in activity-dependent refinement of inhibitory neuronal circuits.
- This finding sheds light on the previously obscure mechanisms guiding inhibitory circuit development.