Presynaptically Silent GABA Synapses in Hippocampus
Date
2005
Authors
Bekkers, John
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Society for Neuroscience
Abstract
Mammalian central synapses commonly specialize in one fast neurotransmitter, matching the content of their presynaptic vesicles with the appropriate receptors in their postsynaptic membrane. Here, I show that hippocampal cultures contain autaptic glutamatergic synapses that contravene this rule: in addition to postsynaptic glutamate receptors, they also express clusters of functional postsynaptic GABAA receptors yet lack presynaptic GABA. Hence, these synapses are presynaptically silent with respect to GABA. They can be unsilenced by loading GABA into presynaptic vesicles by endocytosis, after which a postload IPSC appears. This IPSC is similar to native IPSCs recorded from GABAergic interneurons in the same cultures. Thus, these "mistargeted" GABAA receptors, which apparently lack a signal that confers synaptic specificity, function almost normally. After GABA loading, glutamatergic miniature postsynaptic currents acquire a slow tail that is mediated by GABAA receptors, showing that synaptic vesicles can accommodate both the usual concentration of native glutamate and a saturating concentration of loaded GABA. After brief Ca2+-dependent exocytosis, endocytosis of GABA can proceed in low-Ca2+ external solution. The amplitude of the postload IPSC declines exponentially with repetitive stimulation as the endocytosed GABA passes through the presynaptic vesicle cycle and is depleted. Hence, by using GABA as an exogenous but physiological tracer, the properties of these presynaptically silent synapses can provide novel insights into the content and cycling of vesicles in presynaptic terminals.
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Keywords: 4 aminobutyric acid A receptor; calcium ion; glutamic acid; presynaptic receptor; animal cell; animal tissue; article; bioaccumulation; cell specificity; controlled study; endocytosis; GABAergic transmission; hippocampus; interneuron; nerve cell culture; Autapse; Culture; Endocytosis; EPSC; IPSC; Synaptic vesicle
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Source
Journal of Neuroscience
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Journal article
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2037-12-31