Synaptic transmission in the hippocampus: critical role for glial cells.
The importance of glial cells in controlling the neuronal microenvironment has been increasingly recognized. We now demonstrate that glial cells play an integral role in hippocampal synaptic transmission by using the glial-specific metabolic blocker fluoroacetate (FAC) to selectively inhibit glial cell function. FAC inhibits evoked intracellular postsynaptic potentials (PSPs; IC50 = 39 microM) as well as population PSPs (IC50 = 65 microM) in field CA1 of the guinea pig hippocampal slice. Spontaneous synaptic transmission is concurrently decreased. These effects are time and dose dependent. ATP concentrations in glial but not neuronal elements are also significantly reduced with FAC treatment. Simultaneous application of the metabolic substrate isocitrate with FAC prevents both the reduction in glial ATP concentrations and the decrease in evoked PSPs. Given that isocitrate is selectively taken up by glia, these data further support a glial specific metabolic action of FAC. Additionally, FAC has no postsynaptic effects as peak responses to iontophoretically applied glutamate are unchanged. However, the decay of both iontophoretic and evoked PSPs are prolonged following FAC treatment suggesting inhibition of glutamate uptake may contribute to the FAC-induced depression of synaptic potentials. These results show, for the first time, that glial cells are critical for maintenance of synaptic transmission and suggest a role for glial cells in the modulation of synaptic efficacy.
Keyser
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Physiology Department, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5603.
Pellmar
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005463:Fluoroacetates / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007478:Iontophoresis; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000502:physiology; D014407:Tumor Cells, Cultured
D005463:Fluoroacetates; D005971:Glutamates; D018698:Glutamic Acid; D000255:Adenosine Triphosphate