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Glycine receptors support excitatory neurotransmitter release in developing mouse visual cortex
Author(s) -
Kunz Portia A.,
Burette Alain C.,
Weinberg Richard J.,
Philpot Benjamin D.
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.241299
Subject(s) - neurotransmitter , glycine receptor , excitatory postsynaptic potential , neurotransmission , neuroscience , glutamate receptor , inhibitory postsynaptic potential , nmda receptor , neurotransmitter receptor , biology , chemistry , glycine , receptor , central nervous system , biochemistry , amino acid
Key points• Cortical glycine receptors (GlyRs) flux chloride based on a local chloride gradient set by chloride transporters; this gradient changes with age. • In acute slices from the developing mouse visual cortex, tonic GlyR activity increases spontaneous excitatory neurotransmitter release in a calcium‐dependent manner. • Glycine transporters, localized mainly to astrocytes, regulate this tonic activity. • After a critical period of early development, GlyRs are no longer tonically active and become hyperpolarizing, inhibiting spontaneous neurotransmitter release. • These results define mechanisms that contribute to baseline neurotransmission during critical periods of neuronal development, and help identify synaptic functions that could be impacted by GlyR dysfunction.Abstract Glycine receptors (GlyRs) are found in most areas of the brain, and their dysfunction can cause severe neurological disorders. While traditionally thought of as inhibitory receptors, presynaptic‐acting GlyRs (preGlyRs) can also facilitate glutamate release under certain circumstances, although the underlying molecular mechanisms are unknown. In the current study, we sought to better understand the role of GlyRs in the facilitation of excitatory neurotransmitter release in mouse visual cortex. Using whole‐cell recordings, we found that preGlyRs facilitate glutamate release in developing, but not adult, visual cortex. The glycinergic enhancement of neurotransmitter release in early development depends on the high intracellular to extracellular Cl − gradient maintained by the Na + –K + –2Cl − cotransporter and requires Ca 2+ entry through voltage‐gated Ca 2+ channels. The glycine transporter 1, localized to glial cells, regulates extracellular glycine concentration and the activation of these preGlyRs. Our findings demonstrate a developmentally regulated mechanism for controlling excitatory neurotransmitter release in the neocortex.