Regulation of the Hippocampal Network by VGLUT3-Positive CCK- GABAergic Basket Cells

Abstract

Hippocampal interneurons release the inhibitory transmitter GABA to regulate excitation, rhythm generation and synaptic plasticity. A subpopulation of GABAergic basket cells co-expresses the GABA/glycine vesicular transporters (VIAAT) and the atypical type III vesicular glutamate transporter (VGLUT3); therefore, these cells have the ability to signal with both GABA and glutamate. GABAergic transmission by basket cells has been extensively characterized but nothing is known about the functional implications of VGLUT3-dependent glutamate released by these cells. Here, using VGLUT3-null mice we observed that the loss of VGLUT3 results in a metaplastic shift in synaptic plasticity at Shaeffer’s collaterals – CA1 synapses and an altered theta oscillation. These changes were paralleled by the loss of a VGLUT3-dependent inhibition of GABAergic current in CA1 pyramidal layer. Therefore presynaptic type III metabotropic could be activated by glutamate released from VGLUT3-positive interneurons. This putative presynaptic heterologous feedback mechanism inhibits local GABAergic tone and regulates the hippocampal neuronal network.

Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3Cre mouse

“…The anti‐vGluT2 antibody () was raised against a GST‐tagged Recombinant protein and validated by western blot (Montana, Ni, Sunjara, Hua, & Parpura, ). The anti‐vGluT3 antibody () was raised against a mouse recombinant peptide and validated by vGluT3 knockout mutants (Fasano et al, ).…”

VGLUT3 gates psychomotor effects induced by amphetamine

“…To delete VGLUT3 in specific neuronal subpopulations, mice carrying a floxed allele of the exon 2 of slc17a8 (VGLUT3 LoxP/LoxP , research resource identifier, RRID:IMSR_EM:05733), the gene coding for VGLUT3, was used (Fasano et al 2017). VGLUT3 LoxP/ LoxP mouse line was established at Phenomin -iCS (Phenomin -Institut Clinique de la Souris, Illkirch, France, RRID:SCR_011021).…”

“…Immunofluorescence experiments were performed to confirm the deletion of VGLUT3 in specific subsets of cells or terminals as previously described (Sakae et al 2015;Fasano et al 2017;Janickova et al 2017). Na€ ıve conditional knockouts mice (n = 3-4 per genotype) were anesthetized with sodium pentobarbital (0.1 mL/10 g body weight) and perfused intracardially with paraformaldehyde [PFA 4%, in phosphate-buffered saline (PBS)].…”

Neuregulin 1 Type I Overexpression Is Associated with Reduced NMDA Receptor–Mediated Synaptic Signaling in Hippocampal Interneurons Expressing PV or CCK

“…It has been proposed that NMDAR function could particularly be impaired in hippocampal and neocortical GABAergic interneurons in the disorder, compromising recurrent inhibition ( Carlén et al, 2012 ; Curley and Lewis, 2012 ; Gilmour et al, 2012 ). Two prominent GABAergic inhibitory interneuron subpopulations, defined by mutually exclusive markers parvalbumin (PV) or cholecystokinin (CCK), are strongly involved through recurrent inhibition in rhythmic network activities in the neocortex and hippocampus ( Cobb et al, 1995 ; Ellender and Paulsen, 2010 ; Manseau et al, 2010 ; Lasztóczi et al, 2011 ; Buzsáki and Wang, 2012 ; Fasano et al, 2017 ; Pelkey et al, 2017 ). Disrupted function of either of these interneuron populations in animal models results in alterations of coordinated neuronal network activities, particularly the synchronous gamma frequency (20–80 Hz) oscillations, and causes behavioral changes associated with the disorder ( Belforte et al, 2010 ; Nakazawa et al, 2012 ; Brown et al, 2014 ; Schmidt et al, 2014 ; Cho et al, 2015 ; Gonzalez-Burgos et al, 2015 ; Schmidt and Mirnics, 2015 ; Huang et al, 2016 ; Del Pino et al, 2017 ; Medrihan et al, 2017 ; Vargish et al, 2017 ).…”