Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 3, Pages 725-731Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3625-07.2008
Keywords
neocortex; kainate; GABA; vesicular release; FM1-43; inhibition; multiphoton excitation microscopy; brain slices
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Funding
- NICHD NIH HHS [P30 HD038985, P30 HD038985-079005, P30-HD38985] Funding Source: Medline
- NINDS NIH HHS [P30-NS47466, P30 NS057098, R01 NS022373, P30-NS57098, R01NS22373, P30 NS047466] Funding Source: Medline
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Inhibitory control of local neuronal circuits is critical for prefrontal cortical functioning. Modulation of inhibitory circuits by several neuromodulators has been demonstrated, but the underlying mechanisms are unclear. Neuromodulator effects on synaptic vesicle recycling have received little attention. Controversy also exists whether different pools of synaptic vesicles underlie spontaneous and activity-dependent vesicle recycling. We therefore investigated the effects of kainate receptor activation on GABA release in rat prefrontal neocortex using electrophysiological and styryl dye imaging techniques in acute neocortical slices. Electrophysiological studies demonstrated that activation of kainate receptors increased the frequency, but not the amplitude of miniature IPSCs, suggesting a presynaptic action. Using styryl dye staining and multiphoton excitation microscopy, we visualized vesicular release from inhibitory GABAergic terminals in prefrontal cortical slices and demonstrate that kainate facilitates GABA release from presynaptic terminals. Our findings also indicate the presence of two pools of GABA-containing vesicles within inhibitory terminals. Kainate modulates both pools but only when vesicles are endocytosed and exocytosed by matching protocols of dye loading, i.e., spontaneous or evoked afferent activity.
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