Glutamate Co-Release by Monoamine Neurons

Trudeau, Louis-Éric; Bo, Grégory Dal; Méndez, José Alfredo Tirado

doi:10.1007/978-0-387-09622-3_8

Cited by 4 publications

(8 citation statements)

References 92 publications

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“…5A). Notably, Cluster 5 showed higher expression of other canonical DA neuron markers, important in the vesicular packaging of DA (i.e.,vesicular monoamine transporter 2, Vmat2), in the regulation of SNc neurons excitability (i.e., G-protein-regulated inward-rectifier potassium 2, Girk2), as well as previously reported genes expressed in midbrain DA neurons, such as vesicular glutamate transporter 2, Vglut2, cocaine-and amphetamine-regulated transcript protein, Cartpt and 5-hydroxytryptamine/serotonin receptor 2B, Htr2b (Ásgrímsdóttir & Arenas, 2020;Carpenter et al, 2020;Doly et al, 2017;El Mestikawy et al, 2011;Trudeau, 2004;Trudeau & El Mestikawy, 2018;Trudeau & Gutiérrez, 2007) (Fig. 5B).…”

Section: Single-cell Transcriptomics Corroborates the Existence Of Ch...mentioning

confidence: 66%

“…Historically, a neuronal subtype is defined by the primary neurotransmitter it releases and its functional properties. With the gradual appreciation that many if not most neuronal types in the CNS and PNS utilize more than one type of neurotransmitter (El Mestikawy et al, 2011; Trudeau, 2004; Trudeau & El Mestikawy, 2018; Trudeau & Gutiérrez, 2007) and with the advent of single-cell transcriptomic approaches, assigning a molecular gene signature is progressively being used to precisely define neuronal sub-classes. In the case of midbrain DA neurons, previous microarray and recent single-cell RNA sequencing (RNAseq) work has revealed extensive heterogeneity including in genes specifying their developmental origin, as well as a battery of genes involved in the synthesis and vesicular packaging of DA, but also of other neurotransmitters including glutamate and various neuropeptides (Gaertner et al, 2022; Kouwenhoven et al, 2020; Poulin et al, 2018; Poulin et al, 2020; Poulin et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Characterizing enteric neurons in Dopamine Transporter (DAT)-Cre reporter mice reveals dopaminergic subtypes with dual-transmitter content

Recinto

Premachandran

Mukherjee

et al. 2023

Preprint

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Dopaminergic neurons (DA) are the predominant cell type in the midbrain that synthesize dopamine, a neurotransmitter implicated in a number of behavioural processes, including motor function, the reward pathway, and satiety. In diseases affecting these neurons, such as in Parkinsons disease (PD), there is growing evidence that the gut-brain axis and selective vulnerability of DA neurons plays a crucial role in disease. Most investigations relating to DA neurons in the gut rely on immunoreactivity to tyrosine hydroxylase (TH) - a rate-limiting enzyme in the production of dopamine. However, the reliability of TH staining as a marker of DA neurons has been questioned in recent years. Our aim is to perform a comprehensive characterization of DA neurons in the gut using a well-accepted reporter mouse line, expressing a fluorescent protein under the dopamine transporter promoter (DAT). Our findings confirm a unique localisation of DA neurons in the gut, and also unveil that there are discrete subtypes of DA neurons in the gut, which we characterised using both immunofluorescence and single cell transcriptomics. We observed distinct subtypes of DAT neurons expressing co-transmitters and modulators; some of them likely co-releasing acetylcholine, and a smaller population likely releasing nitric oxide; while others were positive for a slew of canonical DA markers (Vmat2, Girk2, Foxa2). Given the clear heterogeneity of DA gut neurons, further investigation is warranted to define their functional signatures and discover their inherent biological differences that put these cells at risk for neurodegeneration.

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Section: Single-cell Transcriptomics Corroborates the Existence Of Ch...mentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Characterizing enteric neurons in Dopamine Transporter (DAT)-Cre reporter mice reveals dopaminergic subtypes with dual-transmitter content

Recinto

Premachandran

Mukherjee

et al. 2023

Preprint

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show abstract

“…Scale bars: 50 μm. Doly et al, 2017;El Mestikawy et al, 2011;Trudeau, 2004;Trudeau & El Mestikawy, 2018;Trudeau & Gutiérrez, 2007) (Figure 5b). Validating our transcriptome observations, we detected immunoreactivity for VMAT2 and GIRK2 in DAT-Cre-tdTomato-expressing neurons within the ganglionated plexuses (Figure 5c).…”

Section: Single-cell Transcriptomics Corroborates the Existence Of Ch...mentioning

confidence: 99%

Characterizing enteric neurons in dopamine transporter (DAT)‐Cre reporter mice reveals dopaminergic subtypes with dual‐transmitter content

Recinto,

Premachandran,

Mukherjee

et al. 2024

Eur J of Neuroscience

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The enteric nervous system (ENS) comprises a complex network of neurons whereby a subset appears to be dopaminergic although the characteristics, roles, and implications in disease are less understood. Most investigations relating to enteric dopamine (DA) neurons rely on immunoreactivity to tyrosine hydroxylase (TH)—the rate‐limiting enzyme in the production of DA. However, TH immunoreactivity is likely to provide an incomplete picture. This study herein provides a comprehensive characterization of DA neurons in the gut using a reporter mouse line, expressing a fluorescent protein (tdTomato) under control of the DA transporter (DAT) promoter. Our findings confirm a unique localization of DA neurons in the gut and unveil the discrete subtypes of DA neurons in this organ, which we characterized using both immunofluorescence and single‐cell transcriptomics, as well as validated using in situ hybridization. We observed distinct subtypes of DAT‐tdTomato neurons expressing co‐transmitters and modulators across both plexuses; some of them likely co‐releasing acetylcholine, while others were positive for a slew of canonical DAergic markers (TH, VMAT2 and GIRK2). Interestingly, we uncovered a seemingly novel population of DA neurons unique to the ENS which was ChAT/DAT‐tdTomato‐immunoreactive and expressed Grp, Calcb, and Sst. Given the clear heterogeneity of DAergic gut neurons, further investigation is warranted to define their functional signatures and decipher their implication in disease.

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“…All animals were divided into the following groups: (1) control animals that received no intervention during the recording period, (2) animals illuminated with 473 nm light after receiving the control virus (AAV5-hsyn-mCherry), (3) animals illuminated with 473 nm light receiving the excitatory virus (AAV5-hsyn-ChR2(H134R)-mCherry) and expressed LTF, (4) animals illuminated with 473 nm light after receiving the excitatory virus but did not express LTF (henceforth known as non-responders), (5) animals illuminated with 473 nm light after receiving the excitatory virus plus terazosin perfusion to elucidate underlying neural mechanisms, (6) animals illuminated with 532 nm light after receiving the inhibitory virus (AAV5hsyn-eNpHR3.0-mCherry), (7) animals illuminated with 532 nm light after receiving the control virus but were paired with the inhibition group for analysis, (8) animals that received CGS21680 perfusion, (9) animals that received CGS21680 perfusion plus terazosin perfusion, (10) animals that received k252a perfusion, and nally (11) animals that received saline perfusion. In all groups, after each experimental paradigm's surgical intervention, animals were left to stabilize for 30-60 minutes to establish a baseline activity for the genioglossus and diaphragm EMG amplitude, ET-CO 2 , and O 2 saturation.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…The LC has been reported to co-release multiple neurotransmitters such as glutamate [9,10]. To determine whether LTF elicited by intermittent LC stimulation is truly mediated by noradrenaline, rats (n = 9) infected with AAV5-hSyn-ChR2(H134R)-mCherry and simultaneously had a microdialysis probe perfusing lactated Ringer's solution into the hypoglossal motor pool.…”

Section: Objective 3 -Can Optical Silencing Of Locus Coeruleus Neuron...mentioning

confidence: 99%

Multiple Hypoxia-Independent Triggers of Upper Airway Long-Term Facilitation

Lui

Tadjali

Peever

2023

Preprint

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The respiratory control system can augment respiratory output following repetitive challenges. For example, repeated airway obstructions can trigger a form of respiratory memory that strengthens inspiratory activity of hypoglossal (XII) motoneurons. This augmentation in respiratory motor output is known as long-term facilitation (LTF) and can be elicited by repeated apneas or bouts of hypoxia. We demonstrate that LTF can be triggered in the absence of repeated apneas or hypoxia by intermittently stimulating locus coeruleus (LC) neurons, or through pharmacological activation of the neurotrophic machinery in XII motoneurons. We used pharmacological and optogenetic approaches to elicit LTF and show that this is mediated by α1-adrenergic receptor-binding at the XII motor pool. We also use optical LC inhibition to reaffirm the importance of the LC in mediating apnea-induced LTF. Lastly, we show that neurotrophic signaling agonists or antagonists applied to XII motoneurons can also be used to elicit or prevent LTF expression, respectively, and acts co-operatively with noradrenaline. These results suggest LTF can be triggered by multiple hypoxia-independent triggers and is mediated by the release of noradrenaline from the LC onto α1-adrenergic receptors on XII motoneurons to trigger plasticity via activation of neurotrophic signaling cascades.

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Glutamate Co-Release by Monoamine Neurons

Cited by 4 publications

References 92 publications

Characterizing enteric neurons in Dopamine Transporter (DAT)-Cre reporter mice reveals dopaminergic subtypes with dual-transmitter content

Characterizing enteric neurons in Dopamine Transporter (DAT)-Cre reporter mice reveals dopaminergic subtypes with dual-transmitter content

Characterizing enteric neurons in dopamine transporter (DAT)‐Cre reporter mice reveals dopaminergic subtypes with dual‐transmitter content

Multiple Hypoxia-Independent Triggers of Upper Airway Long-Term Facilitation

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