Role of the vesicular transporter VGLUT3 in retrograde release of glutamate by cerebellar Purkinje cells

Abstract

In the cerebellum, retrograde release of glutamate (Glu) by Purkinje cells (PCs) participates in the control of presynaptic neurotransmitter release responsible for the late component of depolarization-induced suppression of excitation (DSE), as well as for depolarization-induced potentiation of inhibition (DPI). It might also participate in the depolarization-induced slow current (DISC) in PCs, although this contribution was later challenged. We also know that both DPI and DISC are soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent processes, although the molecular nature of the vesicular transporter was not determined. In PCs, VGLUT3 is the only known vesicular glutamate transporter identified and is expressed during the same developmental frame as when DPI, DISC, and the Glu-dependent component of DSE are observed. We therefore tested the hypothesis that all these processes depend on the presence of VGLUT3 by comparing the Glu-dependent component of DSE, DPI, and DISC in nearly mature (2-to 3-wk-old) wild-type and VGLUT3 knockout mice. Our data demonstrate that, in nearly mature mice, the slow component of DSE occurs through vesicular release of Glu that involves VGLUT3. This Glu-dependent component of DSE is no longer present in fully mature mice. This study also establishes that, in nearly mature mice, DPI also depends on the presence of VGLUT3, whereas this is not the case for DISC. Finally, the unusually large basal paired-pulse facilitation observed in nearly mature VGLUT3 Ϫ/Ϫ mice but not in adult ones suggests that some basal retrograde release of Glu occurs during development and contributes to basal concentrations of extracellular Glu. depolarization; parallel fibers; postsynaptic currents RETROGRADE SIGNALING THAT allows presynaptic control of neurotransmitter release by postsynaptic elements is now well established at both inhibitory and excitatory synapses. At inhibitory synapses impinging onto hippocampal pyramidal cells and onto cerebellar Purkinje cells (PCs), the so-called depolarization-induced suppression of inhibition (DSI; Glitsch et al.

A New Player in the Hippocampus: A Review on VGLUT3+ Neurons and Their Role in the Regulation of Hippocampal Activity and Behaviour

“…Interestingly, VGLUT3 has the ability to signal retrogradely [ 5 , 70 ]. Crepel et al showed that cerebellar principle cells utilise Glu released from VGLUT3 containing vesicles to retrogradely signal and regulate incoming signals.…”

Synaptic Adaptations at the Rostromedial Tegmental Nucleus Underlie Individual Differences in Cocaine Avoidance Behavior

“…These results are all consistent with higher CP-AMPARs in RMTg in the saline and high-avoider groups compared with low avoiders. However, those experiments used electrically evoked eEPSCs, whose amplitudes could be confounded by known effects on presynaptic release of the many postsynaptic depolarization steps used in our R.I. tests (Kreitzer and Regehr, 2001;Wilson and Nicoll, 2001;Ohno-Shosaku et al, 2002;Kreitzer and Malenka, 2005;Crepel and Daniel, 2007;Crépel et al, 2011). Hence, to control for possible presynaptic differences in electrically evoked glutamate, we repeated the R.I. tests using photolytically uncaged glutamate while blocking presynaptic transmission with TTX.…”