Glutamate Corelease Promotes Growth and Survival of Midbrain Dopamine Neurons

Fortin, Guillaume; Bourque, Marie‐Josée; Mendez, José Alfredo; Leo, Damiana; Nordenankar, Karin; Birgner, Carolina; Arvidsson, Emma; Rymar, Vladimir V.; Bérubé-Carrière, Noémie; Claveau, Anne-Marie; Descarries, Laurent; Sadikot, Abbas F.; Wallén-Mackenzie, Åsa; Trudeau, Louis-Éric

doi:10.1523/jneurosci.1939-12.2012

Cited by 79 publications

(127 citation statements)

References 49 publications

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“…Much of the initial work targeting this population was aimed at deciphering the function of VGLUT2 in dopamine neurons; and conditional disruption of VGLUT2 from dopamine neurons resulted in reductions in psychostimulant-induced locomotion and evoked dopamine release3505152. However, the majority of VGLUT2 + neurons detected in mouse VTA are not dopaminergic29, suggesting that the conditional knockout of VGLUT2 selectively from dopamine neurons left glutamate signalling from VTA neurons largely intact.…”

Section: Discussionmentioning

confidence: 99%

Ventral tegmental area glutamate neurons co-release GABA and promote positive reinforcement

et al. 2016

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In addition to dopamine neurons, the ventral tegmental area (VTA) contains GABA-, glutamate- and co-releasing neurons, and recent reports suggest a complex role for the glutamate neurons in behavioural reinforcement. We report that optogenetic stimulation of VTA glutamate neurons or terminals serves as a positive reinforcer on operant behavioural assays. Mice display marked preference for brief over sustained VTA glutamate neuron stimulation resulting in behavioural responses that are notably distinct from dopamine neuron stimulation and resistant to dopamine receptor antagonists. Whole-cell recordings reveal EPSCs following stimulation of VTA glutamate terminals in the nucleus accumbens or local VTA collaterals; but reveal both excitatory and monosynaptic inhibitory currents in the ventral pallidum and lateral habenula, though the net effects on postsynaptic firing in each region are consistent with the observed rewarding behavioural effects. These data indicate that VTA glutamate neurons co-release GABA in a projection-target-dependent manner and that their transient activation drives positive reinforcement.

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Section: Discussionmentioning

confidence: 99%

Ventral tegmental area glutamate neurons co-release GABA and promote positive reinforcement

et al. 2016

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“…Indeed, mice with a DA neuron conditional VGLUT2 deletion show an attenuated response to psychostimulants (63, 125). While this may be due to the dependence of DA neuron development on VGLUT2 expression (126), it may be due also to vesicular synergy. VGLUT2 mediates vesicular uptake of glutamate, which acting as a counter ion may enhance dopamine packaging, and confer increased sensitivity to amphetamine action.…”

Section: Regional Differences In Psychotropic Drug Action At Striatalmentioning

confidence: 99%

Heterogeneity in Dopamine Neuron Synaptic Actions Across the Striatum and Its Relevance for Schizophrenia

Chuhma

Mingote

Kalmbach

et al. 2017

Biological Psychiatry

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Brain imaging has revealed alterations in dopamine uptake, release and receptor levels in patients with schizophrenia that have been resolved at the scale of striatal subregions. However, the underlying synaptic mechanisms are at a finer scale. Dopamine neuron synaptic actions vary across the striatum, involving not only variations in dopamine release, but also in dopamine neuron connectivity, cotransmission, modulation and activity. Optogenetic studies have revealed that dopamine neurons release dopamine in a synaptic signal mode, and that the neurons also release glutamate and GABA as cotransmitters, with striking regional variation. Fast glutamate and GABA cotransmission convey discrete patterns of dopamine neuron activity to striatal neurons. Glutamate may function not only in a signaling role at a subset of dopamine neuron synapses, but also in mediating vesicular synergy, contributing to regional differences in loading of dopamine into synaptic vesicles. Regional differences in dopamine neuron signaling are likely to be differentially involved in the schizophrenia disease process, and likely determine the subregional specificity of the action of psychostimulants that exacerbate the disorder, and antipsychotics that ameliorate the disorder. Elucidating dopamine neuron synaptic signaling offers the potential for achieving greater pharmacological specificity through intersectional pharmacological actions targeting subsets of dopamine neuron synapses.

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“…Mechanistically, expression of the vesicular glutamate transporter is thought to dissipate the vesicle potential while maximizing the pH gradient used to package monoamines, thereby increasing the concentration of monoamine in the vesicle and enhancing monoaminergic transmission [4,55 •• ]. For example, conditional knockout of the vesicular glutamate transporter in dopaminergic neurons caused behavioral deficits associated with dopaminergic transmission, as well as a reduction in the electrochemical detection of dopamine in the VTA [55 •• ,58–60]. Vesicular synergy also occurs in cholinergic neurons, as VGLUT conditional knockouts have a hypocholinergic phenotype [61].…”

Section: The Spectrum Of Co-release and Co-transmissionmentioning

confidence: 99%

Dual-transmitter neurons: functional implications of co-release and co-transmission

Vaaga

Borisovska

Westbrook

2014

Current Opinion in Neurobiology

163

132

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Co-transmission, the ability of a neuron to release multiple transmitters, has long been recognized in selected circuits. However, the release of multiple primary neurotransmitters from a single neuron is only beginning to be appreciated. Here we consider recent examples of co-transmission as well as co-release – the packaging of multiple neurotransmitters into a single vesicle. The properties associated with each mode of release greatly enhance the possible action of such neurons within circuits. The functional importance of dual- (or multi-) transmitter neurons extends beyond actions on postsynaptic receptors, due in part to differential spatial and temporal profiles of each neurotransmitter. Recent evidence also suggests that the dual-transmitter phenotype can be dynamically regulated during development and following injury or disease.

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Glutamate Corelease Promotes Growth and Survival of Midbrain Dopamine Neurons

Cited by 79 publications

References 49 publications

Ventral tegmental area glutamate neurons co-release GABA and promote positive reinforcement

Ventral tegmental area glutamate neurons co-release GABA and promote positive reinforcement

Heterogeneity in Dopamine Neuron Synaptic Actions Across the Striatum and Its Relevance for Schizophrenia

Dual-transmitter neurons: functional implications of co-release and co-transmission

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