title: Kainate modulates presynaptic GABA release from two vesicle pools.
abstract: 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.
authors.affiliation: Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Seena S
authors.initials: SS
authors.lastname: Mathew
authors.forename: Lucas
authors.initials: L
authors.lastname: Pozzo-Miller
authors.forename: John J
authors.initials: JJ
authors.lastname: Hablitz
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D007608:Kainic Acid / Q000494:pharmacology*; D019579:Neocortex / Q000166:cytology; D018408:Patch-Clamp Techniques / Q000379:methods; D011188:Potassium / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000528:radiation effects; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018690:Excitatory Amino Acid Agonists; C073804:FM1 43; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D000241:Adenosine; D011188:Potassium; D007608:Kainic Acid