Release of chemical transmitters from cell bodies and dendrites of nerve cells

De‐Miguel, Francisco F.; Nicholls, John G.

doi:10.1098/rstb.2014.0181

Cited by 17 publications

(16 citation statements)

References 44 publications

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“…Further, to support this assumption, here we show the simultaneous [ 3 H]Glu efflux in response to an identical optogenetic stimulation ( Figure 4G ). Because light stimulation-evoked 5-HT efflux was sensitive to TTX, the released 5-HT and Glu are probably originated from distinct nerve terminal populations and 5-HT might also be derived from dendrites and cell bodies ( De-Miguel and Nicholls, 2015 ). It is well known that 5-HT is secreted from the somata and dendrites of neurons in the raphe nuclei in response to the activation of NMDA receptors in a [Ca 2+ ] o -dependent way ( de Kock et al, 2006 ; Harsing, 2006 ), and the majority of 5-HT is released in a non-synaptic manner ( Harsing, 2006 ; Vizi et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Hippocampal 5-HT Release by P2X7 Receptors in Response to Optogenetic Stimulation of Median Raphe Terminals of Mice

Gölöncsér

Baranyi

Balázsfi

et al. 2017

Front. Mol. Neurosci.

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Serotonergic and glutamatergic neurons of median raphe region (MRR) play a pivotal role in the modulation of affective and cognitive functions. These neurons synapse both onto themselves and remote cortical areas. P2X7 receptors (P2rx7) are ligand gated ion channels expressed by central presynaptic excitatory nerve terminals and involved in the regulation of neurotransmitter release. P2rx7s are implicated in various neuropsychiatric conditions such as schizophrenia and depression. Here we investigated whether 5-HT release released from the hippocampal terminals of MRR is subject to modulation by P2rx7s. To achieve this goal, an optogenetic approach was used to selectively activate subpopulation of serotonergic terminals derived from the MRR locally, and one of its target area, the hippocampus. Optogenetic activation of neurons in the MRR with 20 Hz was correlated with freezing and enhanced locomotor activity of freely moving mice and elevated extracellular levels of 5-HT, glutamate but not GABA in vivo. Similar optical stimulation (OS) significantly increased [3H]5-HT and [3H]glutamate release in acute MRR and hippocampal slices. We examined spatial and temporal patterns of [3H]5-HT release and the interaction between the serotonin and glutamate systems. Whilst [3H]5-HT release from MRR neurons was [Ca2+]o-dependent and sensitive to TTX, CNQX and DL-AP-5, release from hippocampal terminals was not affected by the latter drugs. Hippocampal [3H]5-HT released by electrical but not OS was subject to modulation by 5- HT1B/D receptors agonist sumatriptan (1 μM), whereas the selective 5-HT1A agonist buspirone (0.1 μM) was without effect. [3H]5-HT released by electrical and optical stimulation was decreased in mice genetically deficient in P2rx7s, and after perfusion with selective P2rx7 antagonists, JNJ-47965567 (0.1 μM), and AZ-10606120 (0.1 μM). Optical and electrical stimulation elevated the extracellular level of ATP. Our results demonstrate for the first time the modulation of 5-HT release from hippocampal MRR terminals by the endogenous activation of P2rx7s. P2rx7 mediated modulation of 5-HT release could contribute to various physiological and pathophysiological phenomena, related to hippocampal serotonergic transmission.

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Section: Discussionmentioning

confidence: 99%

Regulation of Hippocampal 5-HT Release by P2X7 Receptors in Response to Optogenetic Stimulation of Median Raphe Terminals of Mice

Gölöncsér

Baranyi

Balázsfi

et al. 2017

Front. Mol. Neurosci.

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“…; Brimblecombe et al . ) – from presynaptic axonal sites into the striatum (De‐Miguel and Nicholls ), as well as from somatodendritic sites into the midbrain (Ford et al . ; Rice and Patel ) – action potential frequency and its pattern, as well as intracellular presynaptic and somatodendritic Ca 2+ levels in fact mediate eventually all physiological functions of SN DA neurons.…”

Section: Impaired Calcium Homeostasis Mitochondrial and Lysosomal Dymentioning

confidence: 99%

“…). In essence, in a negative feedback loop and via D2‐ARs, dopamine itself modulates and adapts its own activity‐dependent, presynaptic, and somatodendritic release from SN DA neurons, and consequently its physiological functions (De‐Miguel and Nicholls ; Rice and Patel ). It is noteworthy, that this D2‐AR/GIRK2 feedback regulation is particularly pronounced in highly vulnerable mature SN DA neurons, compared to more resistant VTA DA neurons (Lammel et al .…”

Section: Ion Channels Define Activity Pattern and Ca2+ Homeostasis Ofmentioning

confidence: 99%

Converging roles of ion channels, calcium, metabolic stress, and activity pattern of Substantia nigra dopaminergic neurons in health and Parkinson's disease

Duda¹,

Pötschke²,

Liss³

2016

Journal of Neurochemistry

136

131

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Dopamine-releasing neurons within the Substantia nigra (SN DA) are particularly vulnerable to degeneration compared to other dopaminergic neurons. The age-dependent, progressive loss of these neurons is a pathological hallmark of Parkinson's disease (PD), as the resulting loss of striatal dopamine causes its major movement-related symptoms. SN DA neurons release dopamine from their axonal terminals within the dorsal striatum, and also from their cell bodies and dendrites within the midbrain in a calcium-and activity-dependent manner. Their intrinsically generated and metabolically challenging activity is created and modulated by the orchestrated function of different ion channels and dopamine D2-autoreceptors. Here, we review increasing evidence that the mechanisms that control activity patterns and calcium homeostasis of SN DA neurons are not only crucial for their dopamine release within a physiological range but also modulate their mitochondrial and lysosomal activity, their metabolic stress levels, and their vulnerability to degeneration in PD. Indeed, impaired calcium homeostasis, lysosomal and mitochondrial dysfunction, and metabolic stress in SN DA neurons represent central converging trigger factors for idiopathic and familial PD. We summarize double-edged roles of ion channels, activity patterns, calcium homeostasis, and related feedback/feed-forward signaling mechanisms in SN DA neurons for maintaining and modulating their physiological function, but also for contributing to their vulnerability in PD-paradigms. We focus on the emerging roles of maintained neuronal activity and calcium homeostasis within a physiological bandwidth, and its modulation by PD-triggers, as well as on bidirectional functions of voltage-gated L-type calcium channels and

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“…However, in contrast to clear synaptic vesicles, dense core vesicles do not require specialized presynaptic machinery for release. Vesicular release of neuropeptides from dendrites and cell bodies has been observed in a variety of neurons, [19][20][21][22][23] including neuronal cell bodies in dorsal root ganglia. 24 Combined with features discussed below, these properties are consistent with the view that neuropeptides yield relatively slow and prolonged actions over a larger area than classical neurotransmitters.…”

Section: Neuropeptide Processing and Releasementioning

confidence: 99%

Overview of Neuropeptides: Awakening the Senses?

2017

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Humans have a diverse collection of neuropeptides that can influence a multitude of activities. There are now over 100 known neuropeptides and probably many more yet to be identified from the over 1000 predicted peptides encoded by the genome. While diverse, peptides generally share three common characteristics: (1) post-translational processing and release from vesicles, (2) activation of cell-surface receptors over a relatively large distance, and (3) modulation of target cells that are often in the brain and periphery. Within the brain, neuropeptides can modulate the activity of co-released neurotransmitters to either increase or decrease the strength of synaptic signaling. Within the periphery, neuropeptides can function similar to peptide hormones and modulate nearly all bodily functions. Given the clear involvement of the neuropeptide CGRP in migraine and the emerging evidence for other peptides, it seems likely that neuropeptides may help “awaken” the senses and contribute to the heightened sensory state of migraine.

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Release of chemical transmitters from cell bodies and dendrites of nerve cells

Abstract: One contribution of 16 to a discussion meeting issue 'Release of chemical transmitters from cell bodies and dendrites of nerve cells'.

Cited by 17 publications

References 44 publications

Regulation of Hippocampal 5-HT Release by P2X7 Receptors in Response to Optogenetic Stimulation of Median Raphe Terminals of Mice

Regulation of Hippocampal 5-HT Release by P2X7 Receptors in Response to Optogenetic Stimulation of Median Raphe Terminals of Mice

Converging roles of ion channels, calcium, metabolic stress, and activity pattern of Substantia nigra dopaminergic neurons in health and Parkinson's disease

Overview of Neuropeptides: Awakening the Senses?

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