Activity-Dependent Vesicular Monoamine Transporter-Mediated Depletion of the Nucleus Supports Somatic Release by Serotonin Neurons

Colgan, Lesley A.; Putzier, Ilva; Levitan, Edwin S.

doi:10.1523/jneurosci.4210-09.2009

Cited by 41 publications

(54 citation statements)

References 29 publications

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“…This distance may determine at least in part the slow time course of secretion, which is similar to that of somatic exocytosis in other types of neurons (Zhang et al, 2007; Kaushalya et al, 2008; Colgan et al, 2009; Patel et al, 2009), and also by excitable endocrine cells (Penner and Neher, 1988; Heinemann et al, 1993; Chow et al, 1996; Rosé et al, 2002). This apparent type of microtubule-coupled transport suggests its dependence on kinesin motors.…”

Section: Discussionmentioning

confidence: 83%

Cycling of Dense Core Vesicles Involved in Somatic Exocytosis of Serotonin by Leech Neurons

Trueta¹,

Kuffler²,

De‐Miguel³

2012

Front. Physio.

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We studied the cycling of dense core vesicles producing somatic exocytosis of serotonin. Our experiments were made using electron microscopy and vesicle staining with fluorescent dye FM1-43 in Retzius neurons of the leech, which secrete serotonin from clusters of dense core vesicles in a frequency-dependent manner. Electron micrographs of neurons at rest or after 1 Hz stimulation showed two pools of dense core vesicles. A perinuclear pool near Golgi apparatuses, from which vesicles apparently form, and a peripheral pool with vesicle clusters at a distance from the plasma membrane. By contrast, after 20 Hz electrical stimulation 47% of the vesicle clusters were apposed to the plasma membrane, with some omega exocytosis structures. Dense core and small clear vesicles apparently originating from endocytosis were incorporated in multivesicular bodies. In another series of experiments, neurons were stimulated at 20 Hz while bathed in a solution containing peroxidase. Electron micrographs of these neurons contained gold particles coupled to anti-peroxidase antibodies in dense core vesicles and multivesicular bodies located near the plasma membrane. Cultured neurons depolarized with high potassium in the presence of FM1-43 displayed superficial fluorescent spots, each reflecting a vesicle cluster. A partial bleaching of the spots followed by another depolarization in the presence of FM1-43 produced restaining of some spots, other spots disappeared, some remained without restaining and new spots were formed. Several hours after electrical stimulation the FM1-43 spots accumulated at the center of the somata. This correlated with electron micrographs of multivesicular bodies releasing their contents near Golgi apparatuses. Our results suggest that dense core vesicle cycling related to somatic serotonin release involves two steps: the production of clear vesicles and multivesicular bodies after exocytosis, and the formation of new dense core vesicles in the perinuclear region.

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Section: Discussionmentioning

confidence: 83%

Cycling of Dense Core Vesicles Involved in Somatic Exocytosis of Serotonin by Leech Neurons

Trueta¹,

Kuffler²,

De‐Miguel³

2012

Front. Physio.

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“…For example, the fluorescent serotonin (5HT) analog 5,7-dihydroxytryptamine (5,7-dHT) can identify 5HT and dopamine neurons in culture due to its uptake by serotonin transporter (SERT) and DAT, respectively. 5,7-dHT has recently been applied to study somatic release of 5HT from serotonergic neurons in brain slice preparations (28). However, this probe is weakly fluorescent, prone to oxidation and toxic.…”

Section: Discussionmentioning

confidence: 99%

Fluorescent dopamine tracer resolves individual dopaminergic synapses and their activity in the brain

Rodriguez

Pereira²,

Borgkvist³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

102

142

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We recently introduced fluorescent false neurotransmitters (FFNs) as optical tracers that enable the visualization of neurotransmitter release at individual presynaptic terminals. Here, we describe a pH-responsive FFN probe, FFN102, which as a polar dopamine transporter substrate selectively labels dopamine cell bodies and dendrites in ventral midbrain and dopaminergic synaptic terminals in dorsal striatum. FFN102 exhibits greater fluorescence emission in neutral than acidic environments, and thus affords a means to optically measure evoked release of synaptic vesicle content into the extracellular space. Simultaneously, FFN102 allows the measurement of individual synaptic terminal activity by following fluorescence loss upon stimulation. Thus, FFN102 enables not only the identification of dopamine cells and their processes in brain tissue, but also the optical measurement of functional parameters including dopamine transporter activity and dopamine release at the level of individual synapses. As such, the development of FFN102 demonstrates that, by bringing together organic chemistry and neuroscience, molecular entities can be generated that match the endogenous transmitters in selectivity and distribution, allowing for the study of both the microanatomy and functional plasticity of the normal and diseased nervous system. dopamine reporter | secretion kinetics | molecular design | multiphoton imaging D opamine neurotransmission plays a key role in habit learning, motivation, reward, and motor function (1), and altered dopamine neurotransmission is associated with disorders such as Parkinson's disease, schizophrenia, and drug addiction (2-4). As a "social" neurotransmitter that overflows relatively long distances beyond its presynaptic terminals, dopamine's extrasynaptic concentration is principally determined by the combination of exocytotic neurotransmitter release and reuptake by the plasma membrane dopamine transporter (DAT) (5). Psychostimulants, such as cocaine and amphetamine (AMPH), increase extracellular dopamine via interactions with DAT.Extracellular dopamine concentration, particularly in the striatum where it is present at high levels, has been characterized by microdialysis (6, 7) and rapid electrochemical detection using carbon fiber cyclic voltammetry (8, 9) and amperometry (10). The excellent temporal resolution of the electrochemical methods is well suited for measuring changes in extrasynaptic dopamine concentration associated with neuronal activity. However, these approaches usually measure the release and reuptake of dopamine from large sets of striatal dopamine release sites and lack the spatial resolution required to study synaptic transmission at the level of individual presynaptic terminals.Optical methods provide vastly improved spatial resolution so that processes by which specific synapses are modulated can be studied. The first group of fluorescent reporters for the study of presynaptic function were the endocytic FM dyes (11), which act as tracers of exocytosis and endocytosis. Thes...

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“…In fact, glutamate could be released from the soma of LSC neurons. There is abundant evidence supporting the concept of somatic/dendritic release for neuropeptides, monoamines and glutamate (Duguid et al, 2007; Colgan et al, 2009; Xia et al, 2009). Moreover, VGLUT 2 immunoreactivity can be observed close to the plasma membrane in non-visceral DRG cell bodies, suggesting somatic glutamate release (Brumovsky et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Some lumbar sympathetic neurons develop a glutamatergic phenotype after peripheral axotomy with a note on VGLUT2-positive perineuronal baskets

Brumovsky

Seroogy

Lundgren

et al. 2011

Experimental Neurology

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Glutamate is the main excitatory neurotransmitter in the nervous system, including in primary afferent neurons. However, to date a glutamatergic phenotype of autonomic neurons has not been described. Therefore, we explored the expression of vesicular glutamate transporters (VGLUTs) type 1, 2 and 3 in lumbar sympathetic chain (LSC) and major pelvic ganglion (MPG) of naïve BALB/C mice, as well as after pelvic nerve axotomy (PNA), using immunohistochemistry and in situ hybridization. Colocalization with activating transcription factor-3 (ATF-3), tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT) and calcitonin generelated peptide was also examined. Sham-PNA, sciatic nerve axotomy (SNA) or naïve mice were included. In naïve mice, VGLUT2-like immunoreactivity (LI) was only detected in fibers and varicosities in LSC and MPG; no ATF-3-immunoreactive (IR) neurons were visible. In contrast, PNA induced upregulation of VGLUT2 protein and transcript, as well as of ATF-3-LI in subpopulations of LSC neurons. Interestingly, VGLUT2-IR LSC neurons coexpressed ATF-3, and often lacked the noradrenergic marker TH. SNA only increased VGLUT2 protein and transcript in scattered LSC neurons. Neither PNA nor SNA upregulated VGLUT2 in MPG neurons. We also found perineuronal baskets immunoreactive either for VGLUT2 or the acetylcholinergic marker VAChT in non-PNA MPGs, usually around TH-IR neurons. VGLUT1-LI was restricted to some varicosities in MPGs, was absent in LSCs, and remained largely unaffected by PNA or SNA. This was confirmed by the lack of expression of VGLUT1 or VGLUT3 mRNAs in LSCs, even after PNA or SNA. Taken together, axotomy of visceral and non-visceral nerves results in a glutamatergic phenotype of some LSC neurons. In addition, we show previously non-described MPG perineuronal glutamatergic baskets.

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Activity-Dependent Vesicular Monoamine Transporter-Mediated Depletion of the Nucleus Supports Somatic Release by Serotonin Neurons

Cited by 41 publications

References 29 publications

Cycling of Dense Core Vesicles Involved in Somatic Exocytosis of Serotonin by Leech Neurons

Cycling of Dense Core Vesicles Involved in Somatic Exocytosis of Serotonin by Leech Neurons

Fluorescent dopamine tracer resolves individual dopaminergic synapses and their activity in the brain

Some lumbar sympathetic neurons develop a glutamatergic phenotype after peripheral axotomy with a note on VGLUT2-positive perineuronal baskets

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