Activity-dependent somatodendritic dopamine release in the substantia nigra autoinhibits the releasing neuron

Hikima, Takuya; Lee, Christian R.; Witkovsky, Paul; Chesler, Julia; Ichtchenko, Konstantin; Rice, Margaret E.

doi:10.1016/j.celrep.2021.108951

Cited by 29 publications

(32 citation statements)

References 89 publications

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“…Whole-cell dialysis 10 mM EGTA fully disinhibited the cocaine-mediated reduction of the firing rate of LC neurons (Figures 4A and 4B), suggesting that local NE release from the recorded LC neuron is sufficient to inhibit its firing activity. This observation is consistent with a recent study revealing that local DA release cell autonomously regulates their activity in substantia nigra pars compacta (SNc) (Hikima et al, 2021). Interestingly, previous studies reported that cocaine-induced hyperpolarization exists in the presence of calcium chelators in the internal solution (Courtney and Ford, 2014;Courtney et al, 2012;Ford et al, 2009); this discrepancy might be due to different experimental conditions such as species (rat versus mouse), animal age (postnatal 8-10 days versus 3-6 weeks), temperature (room temperature versus physiological temperature), and cell types (DA neurons versus LC-NE neurons).…”

Section: Discussionsupporting

confidence: 93%

Cocaine increases quantal norepinephrine secretion through NET-dependent PKC activation in locus coeruleus neurons

Zhu

Liu²,

Li³

et al. 2022

Cell Reports

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Section: Discussionsupporting

confidence: 93%

Cocaine increases quantal norepinephrine secretion through NET-dependent PKC activation in locus coeruleus neurons

Zhu

Liu²,

Li³

et al. 2022

Cell Reports

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“…The dendrites of dopamine neurons perform roles traditionally associated with axons, reliably backpropagating action potentials (Hage and Khaliq, 2015; Hausser et al, 1995) and releasing dopamine (Beckstead et al, 2004; Gantz et al, 2013; Gantz et al, 2018; Hikima et al, 2021; Lebowitz et al, 2021). In this study we reveal properties of DA axons that are reminiscent of dendritic functions.…”

Section: Discussionmentioning

confidence: 99%

Fast synaptic-like axo-axonal transmission from striatal cholinergic interneurons onto dopaminergic fibers

Kramer¹,

Brill-Weil²,

Cummins³

et al. 2022

Preprint

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Transmission from striatal cholinergic interneurons (CINs) controls dopamine release through nicotinic acetylcholine receptors (nAChRs) on dopaminergic axons. Anatomical studies suggest that cholinergic terminals signal predominantly through non-synaptic volume transmission. However, the influence of cholinergic transmission on electrical signaling in axons remains unclear. We examined axo-axonal transmission from CINs onto dopaminergic axons using perforated-patch recordings which revealed rapid spontaneous EPSPs with properties characteristic of fast synapses. Pharmacology showed that axonal EPSPs (axEPSPs) were mediated primarily by high-affinity α6-containing receptors. Remarkably, axEPSPs triggered spontaneous action potentials locally in dopaminergic axons, suggesting these axons perform integration to convert synaptic input into spiking, a function associated with somatodendritic compartments. We investigated cross-species validity of cholinergic axo-axonal transmission by recording dopaminergic axons in macaque putamen and found similar axEPSPs. Thus, we reveal that fast synaptic-like neurotransmission underlies cholinergic signaling onto dopaminergic axons, providing insight into how nicotinic receptors shape electrical signaling directly in axon terminals.

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“…Therefore, dopamine-releasing neurons are unlikely to cause excitotoxicity in medium spiny neurons [ 36 , 37 ]. In addition, nigrostriatal dopaminergic neurons themselves express D2R, and the released dopamine is thought to exert autocrine inhibitory effects on the excitability of these neurons [ 38 , 39 , 40 ]. Dopaminergic neurons perform the tonic release of dopamine according to the pacemaking activity and switch to phasic release when necessary; the released dopamine may exert negative feedback on dopaminergic neurons.…”

Section: Dopaminergic Neurons and Astrocytesmentioning

confidence: 99%

Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease

Takahashi

Mashima

2022

Antioxidants

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Oxidative stress and neuroinflammation are common bases for disease onset and progression in many neurodegenerative diseases. In Parkinson disease, which is characterized by the degeneration of dopaminergic neurons resulting in dopamine depletion, the pathogenesis differs between hereditary and solitary disease forms and is often unclear. In addition to the pathogenicity of alpha-synuclein as a pathological disease marker, the involvement of dopamine itself and its interactions with glial cells (astrocyte or microglia) have attracted attention. Pacemaking activity, which is a hallmark of dopaminergic neurons, is essential for the homeostatic maintenance of adequate dopamine concentrations in the synaptic cleft, but it imposes a burden on mitochondrial oxidative glucose metabolism, leading to reactive oxygen species production. Astrocytes provide endogenous neuroprotection to the brain by producing and releasing antioxidants in response to oxidative stress. Additionally, the protective function of astrocytes can be modified by microglia. Some types of microglia themselves are thought to exacerbate Parkinson disease by releasing pro-inflammatory factors (M1 microglia). Although these inflammatory microglia may further trigger the inflammatory conversion of astrocytes, microglia may induce astrocytic neuroprotective effects (A2 astrocytes) simultaneously. Interestingly, both astrocytes and microglia express dopamine receptors, which are upregulated in the presence of neuroinflammation. The anti-inflammatory effects of dopamine receptor stimulation are also attracting attention because the functions of astrocytes and microglia are greatly affected by both dopamine depletion and therapeutic dopamine replacement in Parkinson disease. In this review article, we will focus on the antioxidative and anti-inflammatory effects of astrocytes and their synergism with microglia and dopamine.

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Activity-dependent somatodendritic dopamine release in the substantia nigra autoinhibits the releasing neuron

Cited by 29 publications

References 89 publications

Cocaine increases quantal norepinephrine secretion through NET-dependent PKC activation in locus coeruleus neurons

Cocaine increases quantal norepinephrine secretion through NET-dependent PKC activation in locus coeruleus neurons

Fast synaptic-like axo-axonal transmission from striatal cholinergic interneurons onto dopaminergic fibers

Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease

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