VTA Glutamate Neuron Activity Drives Positive Reinforcement Absent Dopamine Co-release

Zell, Vivien; Steinkellner, Thomas; Hollon, Nick G.; Warlow, Shelley M.; Souter, Elizabeth; Faget, Lauren; Hunker, Avery C.; Jin, Xin; Zweifel, Larry S.; Hnasko, Thomas S.

doi:10.1016/j.neuron.2020.06.011

Cited by 99 publications

(116 citation statements)

References 60 publications

(82 reference statements)

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“…While often the receptor involved in a particular behavior has been identified, the nature and timing of signal and subsequent activation remain elusive. And finally, it is well known that DANs can co-release other neurotransmitters such as GABA or glutamate (Zell et al 2020). How is a coordinated or perhaps even more difficult to explain, alternative release of dopamine and another transmitter controlled?…”

Section: Discussionmentioning

confidence: 99%

Dopamine modulation of sensory processing and adaptive behavior in flies

2021

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Behavioral flexibility for appropriate action selection is an advantage when animals are faced with decisions that will determine their survival or death. In order to arrive at the right decision, animals evaluate information from their external environment, internal state, and past experiences. How these different signals are integrated and modulated in the brain, and how context- and state-dependent behavioral decisions are controlled are poorly understood questions. Studying the molecules that help convey and integrate such information in neural circuits is an important way to approach these questions. Many years of work in different model organisms have shown that dopamine is a critical neuromodulator for (reward based) associative learning. However, recent findings in vertebrates and invertebrates have demonstrated the complexity and heterogeneity of dopaminergic neuron populations and their functional implications in many adaptive behaviors important for survival. For example, dopaminergic neurons can integrate external sensory information, internal and behavioral states, and learned experience in the decision making circuitry. Several recent advances in methodologies and the availability of a synaptic level connectome of the whole-brain circuitry of Drosophila melanogaster make the fly an attractive system to study the roles of dopamine in decision making and state-dependent behavior. In particular, a learning and memory center—the mushroom body—is richly innervated by dopaminergic neurons that enable it to integrate multi-modal information according to state and context, and to modulate decision-making and behavior.

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Section: Discussionmentioning

confidence: 99%

Dopamine modulation of sensory processing and adaptive behavior in flies

2021

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“…Neurons that release both classical transmitters, like glutamate, and biogenic amines, like tyramine, can employ them additively, cooperatively, or distinctly. In mice, dopaminergic neurons that project from the ventral tegmental area to the nucleus accumbens release both dopamine and glutamate, and either transmitter can support positive reinforcement (Zell et al, 2020). In both Drosophila and mice, the glutamate transporter enhances dopamine loading into synaptic vesicles for a cooperative effect (Aguilar et al, 2017; Munster-Wandowski et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Neurons coordinate their activity across networks using a variety of signals: fast chemical transmitters, biogenic amines, neuropeptides, and electrical coupling via gap junctions (Tritsch & Sabatini, 2012; Zell et al, 2020; Taylor et al, 2019; P. Liu et al, 2017; Nagy et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Behavioral control by depolarized and hyperpolarized states of an integrating neuron by

Sordillo

Bargmann

2021

Preprint

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Coordinated transitions between mutually exclusive motor states are central to behavioral decisions. During locomotion, the nematode Caenorhabditis elegans spontaneously cycles between forward runs, reversals, and turns with complex but predictable dynamics. Here we provide insight into these dynamics by demonstrating how RIM interneurons, which are active during reversals, act in two modes to stabilize both forward runs and reversals. By systematically quantifying the roles of RIM outputs during spontaneous behavior, we show that RIM lengthens reversals when depolarized through glutamate and tyramine neurotransmitters and lengthens forward runs when hyperpolarized through its gap junctions. RIM is not merely silent upon hyperpolarization: RIM gap junctions reinforce a hyperpolarized state of the reversal circuit that inhibits reversals. Additionally, the combined outputs of chemical synapses and gap junctions from RIM jointly regulate forward-to-reversal transitions. Our results indicate that multiple classes of RIM synapses create behavioral inertia during spontaneous locomotion.

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“…As noted, a subset of VTA glutamate neurons are capable of releasing other neurotransmitters depending on projection target. For example, a minority (~10-20%) of all VTA glutamate neurons expresses the dopamine marker TH, however those VTA glutamate neurons that project to the NAc appear to express VGLUT2 at much higher rates (>70%) (Yamaguchi et al, 2011;Zell et al, 2020). Thus most of the synapses we assessed in NAc are likely to be derived from VTA dopamine neurons that co-express VGLUT2:miniSOG, and this presumably accounts for our widespread identification of en passant synapses typical of dopamine neurons in NAc (Descarries et al, 2008;Descarries and Mechawar, 2000;Descarries et al, 1996;Nirenberg et al, 1996;Sesack et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…For example, some VTA neurons express both VGLUT2 and the vesicular monoamine transporter (VMAT2) and release glutamate and dopamine (Chuhma et al, 2004;Hnasko et al, 2010;Kawano et al, 2006;Stuber et al, 2010;Tecuapetla et al, 2010;Yamaguchi et al, 2015); while others express VGLUT2 and the vesicular GABA transporter (VGAT) and release both glutamate and GABA (Root et al, 2014;Yoo et al, 2016). The function of VTA dopamine neurons in reward learning and motivation is well known, but VTA glutamate neurons have also been implicated in processes regulating reward, approach and avoidance behaviors (Alsio et al, 2011;Mingote et al, 2019;Root et al, 2018;Yoo et al, 2016;Zell et al, 2020). Like VTA dopamine neurons, VTA glutamate neurons project to nucleus accumbens (NAc), frontal cortex, and amygdala, but also project to forebrain regions that receive little dopamine input including ventral pallidum (VP) and lateral habenula (LHb) (Hnasko et al, 2012;Taylor et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

A genetic probe for visualizing glutamatergic synapses and vesicles by 3D electron microscopy

Steinkellner

Madany

Haberl

et al. 2020

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Communication between neurons relies on the release of diverse neurotransmitters, which represent a key-defining feature of a neuron's chemical and functional identity. Neurotransmitters are packaged into vesicles by specific vesicular transporters. However, tools for labeling and imaging synaptic vesicles based on their neurochemical identity remain limited. We developed a genetically encoded probe to identify glutamatergic synaptic vesicles at the levels of both light and electron microscopy (EM) by fusing the mini singlet oxygen generator (miniSOG) probe to an intra-lumenal loop of the vesicular glutamate transporter-2. We then used a 3D imaging method, serial block face scanning EM, combined with a deep learning approach for automatic segmentation of labeled synaptic vesicles to assess the subcellular distribution of transporter-defined vesicles at nanometer scale. These tools represent a new resource for accessing the subcellular structure and molecular machinery of neurotransmission and for transmitter-defined tracing of neuronal connectivity.

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VTA Glutamate Neuron Activity Drives Positive Reinforcement Absent Dopamine Co-release

Cited by 99 publications

References 60 publications

Dopamine modulation of sensory processing and adaptive behavior in flies

Dopamine modulation of sensory processing and adaptive behavior in flies

Behavioral control by depolarized and hyperpolarized states of an integrating neuron by

A genetic probe for visualizing glutamatergic synapses and vesicles by 3D electron microscopy

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