Extrasynaptic Vesicular Transmitter Release from the Somata of Substantia Nigra Neurons in Rat Midbrain Slices

Jaffe, E. H.; Marty, Alain; Schulte, Albert; Chow, Robert H.

doi:10.1523/jneurosci.18-10-03548.1998

Cited by 186 publications

(169 citation statements)

References 22 publications

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“…Fusing secretory vesicles outside synapses have previously been observed in dendrites using electron microscopy (Zhu et al, 1986) and live imaging (Hartmann et al, 2001), and from the somata of substantia nigra neurons using amperometry (Jaffe et al, 1998). Although overexpression of cargo may influence the synaptic/extrasynaptic ratio, these data confirm that secretory granule release does not require a specialized active zone and that fusogenic SNARE complexes exist outside synapses.…”

Section: Stable Deposit Of Cargo Is Consistent With Biological Functionsupporting

confidence: 66%

Matrix-Dependent Local Retention of Secretory Vesicle Cargo in Cortical Neurons

Wit¹,

Toonen²,

Verhage³

2009

J. Neurosci.

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Neurons secrete many diffusible signals from synaptic and other secretory vesicles. We characterized secretion of guidance cues, neuropeptides, neurotrophins, and proteases from single secretory vesicles using pHluorin-tagged cargo in cortical neurons. Stimulation triggered transient and persistent fusion events. Transient events represented full release followed by cargo diffusion or incomplete release followed by vesicle retrieval, as previously observed in neuroendocrine cells. Unexpectedly, we also observed that certain cargo, such as Semaphorin 3A (Sema3A), was delivered at the cell surface as stable deposits. Stable deposits and transient events were observed for single cargo and both were SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) and calcium dependent. The ratio between stable and transient events did not depend on cargo size, subcellular localization (synaptic vs extrasynaptic secretion), or the presence of the extracellular matrix. Instead, the ratio is cargo specific and depends on an interaction with the vesicle matrix through a basic domain in the cargo protein. Inhibition of this interaction through deletion of the basic domain in Sema3A abolished stable deposits and rendered all events transient. Strikingly, cargo favoring transient release was stably deposited after corelease with cargo favoring stable deposit. These data argue against cargo diffusion after exocytosis as a general principle. Instead, the vesicle matrix retains secreted signals, probably for focal signaling at the cell surface.

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Section: Stable Deposit Of Cargo Is Consistent With Biological Functionsupporting

confidence: 66%

Matrix-Dependent Local Retention of Secretory Vesicle Cargo in Cortical Neurons

Wit¹,

Toonen²,

Verhage³

2009

J. Neurosci.

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“…For instance, in the substantia nigra, dopamine is released within the nucleus (Cheramy et al, 1981;Jaffe et al, 1998). Interestingly, dopamine acts on presynaptic GABAergic terminals (Radnikow and Misgeld, 1998).…”

Section: Somatodendritic Secretion Of Retrograde Transmittersmentioning

confidence: 99%

Somatodendritic Secretion in Oxytocin Neurons Is Upregulated during the Female Reproductive Cycle

Kock¹,

Wierda²,

Bosman³

et al. 2003

J. Neurosci.

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During the female reproductive cycle, hypothalamic oxytocin (OT) neurons undergo sharp changes in excitability. In lactating mammals, bursts of electrical activity of OT neurons result in the release of large amounts of OT in the bloodstream, which causes milk ejection. One hypothesis is that OT neurons regulate their own firing activity and that of nearby OT neurons by somatodendritic release of OT. In this study, we show that OT neuron activity strongly reduces inhibitory synaptic transmission to these neurons. This effect is blocked by antagonists of both adenosine and OT receptors and is mimicked by OT application. Inhibition of soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex formation by tetanus toxin completely blocked the stimulation-induced reduction in inhibitory input, as did the calcium chelator BAPTA. During lactation, the readily releasable pool of secretory vesicles in OT cell bodies was doubled, and calcium currents were upregulated. This resulted in an increased inhibition of GABAergic synaptic transmission by somatodendritic release during lactation compared with the adult virgin stage. These results demonstrate that somatodendritic release is augmented during lactation, which is a novel form of plasticity to change the strength of synaptic transmission.

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“…Much additional DA signaling occurs more rapidly and on finer spatial scales where synaptic events take place. [15][16][17] Thus, there are reasons to pause and reanalyze even valued hypotheses. On the other hand, the interpretations of Laviolette and van der Kooy also can be questioned.…”

Section: Another Wrinkle In the Nicotine Addiction Storymentioning

confidence: 99%

Roles of dopamine signaling in nicotine addiction

Dani¹

2003

Mol Psychiatry

122

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More than 3 million deaths a year are attributable to smoking worldwide, and the use of tobacco is on the rise in developing countries. Consequently, tobacco use is one of the few causes of mortality that is increasing, with deaths projected to reach 10 million annually in 30-40 years. 1 In developed countries, smoking is presently estimated to cause 20% of all deaths, making it the largest single cause of preventable death. In the United States alone, smokingrelated illness causes more than 430 000 deaths and $150 billion in medical costs and lost productivity annually. 2 Nicotine is the primary addictive component of tobacco. [3][4][5][6][7] It motivates smoking by about 1.1 billion people, representing approximately one-third of the global population aged 15 and over. 8 The addictive power of tobacco is exemplified by the difficulty in quitting. Most attempts to quit smoking fail, and success is usually achieved only after repeated attempts. In the United States, nearly three-fourth of adult smokers want to stop. About one-third of these smokers try to quit each year, but only a few percent succeed. 9 Since it is such a serious health problem, nicotine addiction arising from tobacco use has been the focus of much research. For nicotine and other psychostimulant drugs of abuse, the accumulation of evidence supports the hypothesis that mesocorticolimbic dopamine (DA) systems mediate the reinforcement for continued drug use despite the harmful consequences. [3][4][5][6]10,11 Useful hypothesis of dopamine signaling in reward-based behaviors Rewards obtained from the environment serve as positive reinforcers that shape behaviors for success. Rewards provide the incentive to achieve goals that can yield pleasure and perpetuate life. Since the environment is variable and achieving desirable goals requires continual adjustments, rewards serve in an ongoing learning process that updates an animal's repertoire of behaviors. Exploiting the environment to achieve the natural rewards of food, shelter and, ultimately, reproductive success has evolutionarily produced important systems in the brain for the processing of reward-based learning. A wide range of studies, including electrical self-stimulation, selfadministration, place preference, in vivo imaging, pharmacology, and cellular electrophysiology have indicated that the neurotransmitter, DA, participates in these reward-based events. 3-6,10,11 Dopaminergic projections originating in the ventral tegmental area (VTA) and innervating the striatum, the amygdala, and the prefrontal cortex compose the mesocorticolimbic DA systems that have been specifically identified to be of primary, but not exclusive, importance.Addictive drugs tap into the reward-related neuronal systems, reinforcing and ultimately solidifying maladaptive behaviors. Years of experimentation have indicated that drugs such as cocaine, amphetamine, and nicotine mediate their reinforcing properties via the mesocorticolimbic DA systems. These drugs are self-administered in controlled animal studies, and the ...

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Extrasynaptic Vesicular Transmitter Release from the Somata of Substantia Nigra Neurons in Rat Midbrain Slices

Cited by 186 publications

References 22 publications

Matrix-Dependent Local Retention of Secretory Vesicle Cargo in Cortical Neurons

Matrix-Dependent Local Retention of Secretory Vesicle Cargo in Cortical Neurons

Somatodendritic Secretion in Oxytocin Neurons Is Upregulated during the Female Reproductive Cycle

Roles of dopamine signaling in nicotine addiction

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