4.5 Article Proceedings Paper

Activity-dependent regulation of vesicular glutamate and GABA transporters: A means to scale quantal size

Journal

NEUROCHEMISTRY INTERNATIONAL
Volume 48, Issue 6-7, Pages 643-649

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2005.12.029

Keywords

VGLUT1; VGLUT2; VIAAT; synaptic plasticity; synaptic vesicle; quantal size; homeostatic plasticity; vesicular transporter; glutamate; GABA

Funding

  1. NCRR NIH HHS [1P29RR16816] Funding Source: Medline
  2. NINDS NIH HHS [NS36936] Funding Source: Medline

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The functional balance of glutamatergic and GABAergic signaling in neuronal cortical circuits is under homeostatic control. That is, prolonged alterations of global network activity leads to opposite changes in quantal amplitude at glutamatergic and GABAergic synapses. Such scaling of excitatory and inhibitory transmission within cortical circuits serves to restore and maintain a constant spontaneous firing rate of pyramidal neurons. Our recent work shows that this includes alterations in the levels of expression of vesicular glutamate (VGLUT1 and VGLUT2) and GABA (VIAAT) transporters. Other vesicle markers, such as synaptophysin or synapsin, are not regulated in this way. Endogenous regulation at the level of mRNA and synaptic protein controls the number of transporters per vesicle and hence, the level of vesicle filling with transmitter. Bidirectional and opposite activity-dependent regulation of VGLUT1 and VIAAT expression would serve to adjust the balance of glutamate and GABA release and therefore the level of postsynaptic receptor saturation. In some excitatory neurons and synapses. co-expression of VGLUT1 and VGLUT2 occurs. Bidirectional and opposite changes in the levels of two excitatory vesicular transporters would enable individual neocortical neurons to scale up or scale down the level of vesicular glutamate storage. and thus, the amount available for release at individual synapses. Regulated vesicular transmitter storage and release via selective changes in the level of expression of vesicular glutamate and GABA transporters indicates that homeostatic plasticity of synaptic strength at cortical synapses includes presynaptic elements. (C) 2006 Elsevier Ltd. All rights reserved.

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