Co-expression of VGLUT1 and VGAT sustains glutamate and GABA co-release and is regulated by activity in cortical neurons.
In adult neocortex, VGLUT1 (also known as SLC17A7), the main glutamate vesicular transporter, and VGAT (also known as SLC32A1), the γ-aminobutyric acid (GABA) vesicular transporter, are co-expressed in a subset of axon terminals forming both symmetric and asymmetric synapses, where they are sorted into the same vesicles. However, the functional consequence of this colocalization in cortical neurons has not been clarified. Here, we tested the hypothesis that cortical axon terminals co-expressing VGLUT1 and VGAT can evoke simultaneously monosynaptic glutamate and GABA responses, and investigated whether the amount of terminals co-expressing VGLUT1 and VGAT is affected by perturbations of excitation-inhibition balance. In rat primary cortical neurons, we found that a proportion of synaptic and autaptic responses were indeed sensitive to consecutive application of selective glutamate and GABAA receptor blockers. These 'mixed' synapses exhibited paired-pulse depression. Notably, reducing the activity of the neuronal network by treatment with glutamate receptor antagonists decreased the amount of 'mixed' synapses, whereas reducing spontaneous inhibition by treatment with bicuculline increased them. These synapses might contribute to homeostatic regulation of excitation-inhibition balance.
Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, 60126 Ancona, Italy Center for Neurobiology of Aging, INRCA IRCCS, 60121 Ancona, Italy.
Giorgia
G
Fattorini
Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milano, Italy CNR Institute of Neuroscience, 20129 Milano, Italy.
Flavia
F
Antonucci
CNR Institute of Neuroscience, 20129 Milano, Italy Istituto Clinico Humanitas, IRCCS, 20089 Rozzano (Milano), Italy.
Elisabetta
E
Menna
CNR Institute of Neuroscience, 20129 Milano, Italy Istituto Clinico Humanitas, IRCCS, 20089 Rozzano (Milano), Italy.
Michela
M
Matteoli
Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, 60126 Ancona, Italy Center for Neurobiology of Aging, INRCA IRCCS, 60121 Ancona, Italy Fondazione di Medicina Molecolare, Università Politecnica delle Marche, 60126 Ancona, Italy f.conti@univpm.it.
Fiorenzo
F
Conti
D000200:Action Potentials; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology*; D018698:Glutamic Acid / Q000378:metabolism*; D007395:Interneurons / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C493466:Slc17a7 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
Co‐release; GABA; Glutamate; VGAT; VGLUT1