Abstract
Activity-dependent synapse refinement is crucial for the formation of precise excitatory and inhibitory neuronal circuits. Whereas the mechanisms that guide refinement of excitatory circuits are becoming increasingly clear, the mechanisms guiding inhibitory circuits have remained obscure. In the lateral superior olive (LSO), a nucleus in the mammalian sound localization system that receives inhibitory input from the medial nucleus of the trapezoid body (MNTB), specific elimination and strengthening of synapses that are both GABAergic and glycinergic (GABA/glycinergic synapses) is essential for the formation of a precise tonotopic map. We provide evidence that immature GABA/glycinergic synapses in the rat LSO also release the excitatory neurotransmitter glutamate, which activates postsynaptic NMDA receptors (NMDARs). Immunohistochemical studies demonstrate synaptic colocalization of the vesicular glutamate transporter 3 with the vesicular GABA transporter, indicating that GABA, glycine and glutamate are released from single MNTB terminals. Glutamatergic transmission at MNTB-LSO synapses is most prominent during the period of synapse elimination. Synapse-specific activation of NMDARs by glutamate release at GABAergic and glycinergic synapses could be important in activity-dependent refinement of inhibitory circuits.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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Amino Acid Transport Systems / metabolism
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Amino Acid Transport Systems, Acidic / metabolism
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Animals
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Animals, Newborn
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Auditory Pathways / drug effects
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Auditory Pathways / growth & development*
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Bicuculline / pharmacology
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Cell Count / methods
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Dose-Response Relationship, Radiation
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Drug Interactions
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Excitatory Postsynaptic Potentials / radiation effects
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GABA Antagonists / pharmacology
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Glycine / metabolism
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Glycine Agents
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Immunohistochemistry / methods
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In Vitro Techniques
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Membrane Glycoproteins / metabolism
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Membrane Transport Proteins / metabolism
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Nerve Tissue Proteins / metabolism
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Neural Inhibition / drug effects
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Neural Inhibition / physiology*
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Neural Inhibition / radiation effects
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Neurons / drug effects
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Neurons / physiology*
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Neurons / radiation effects
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Olivary Nucleus / cytology*
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Olivary Nucleus / growth & development*
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Patch-Clamp Techniques / methods
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Rats
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Receptors, N-Methyl-D-Aspartate / physiology
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Strychnine / pharmacology
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Synapses / drug effects
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Synapses / physiology*
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Synapses / radiation effects
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Vesicular Glutamate Transport Protein 1
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Vesicular Glutamate Transport Proteins
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Vesicular Inhibitory Amino Acid Transport Proteins
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Vesicular Transport Proteins / metabolism
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gamma-Aminobutyric Acid / metabolism*
Substances
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Amino Acid Transport Systems
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Amino Acid Transport Systems, Acidic
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Excitatory Amino Acid Antagonists
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GABA Antagonists
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Glycine Agents
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Receptors, N-Methyl-D-Aspartate
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Slc17a8 protein, rat
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Slc32a1 protein, rat
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Sv2a protein, rat
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Vesicular Glutamate Transport Protein 1
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Vesicular Glutamate Transport Proteins
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Vesicular Inhibitory Amino Acid Transport Proteins
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Vesicular Transport Proteins
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gamma-Aminobutyric Acid
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6-Cyano-7-nitroquinoxaline-2,3-dione
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2-Amino-5-phosphonovalerate
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Strychnine
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Glycine
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Bicuculline