Prominent Burst Firing of Dopaminergic Neurons in the Ventral Tegmental Area during Paradoxical Sleep

Dahan, Lionel; Astier, Bernadette; Vautrelle, Nicolas; Urbain, Nadia; Kocsis, Bernát; Chouvet, Guy

doi:10.1038/sj.npp.1301251

Cited by 255 publications

(193 citation statements)

References 96 publications

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“…Such a response pattern has been previously shown on presumed DA VTA neurons during active wakefulness and paradoxical sleep compared to slow-wave sleep (Dahan et al, 2007). Because of this, the excitatory effect of tail-press was significant not only for all LS cells, but also for a subgroup of "nonresponders" (see Fig.…”

Section: Sensory Responses Of Ls and Ss Vta Neuronssupporting

confidence: 71%

“…In contrast to the striatum, which is comprised of primarily GABA-containing spiny cells (Parent and Hazrati, 1995), VTA neuronal population is highly heterogeneous, with cells containing many different neurotransmitters (DA, GABA, glutamate or GLU, peptides) (Bjorklund and Lindvall, 1984;Swanson, 1982). Although VTA cells were extensively studied in vitro and anesthetized preparations (Chiodo, 1988;Grace and Bunney, 1984), data in awake conditions are limited and point at the high variability in their electrophysiological properties and important differences in their activity and responsiveness to sensory stimuli (Dahan et al, 2007;Freeman et al, 1985;Horvitz et al, 1997;Kiyatkin, 1988;Rebec, 1998, 2001;Schultz, 1986). By recording impulse activity of single VTA neurons following iv cocaine administration and tail-press stimulation, we tried to answer two primary questions.…”

Section: Introductionmentioning

confidence: 99%

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Sensory effects of intravenous cocaine on dopamine and non-dopamine ventral tegmental area neurons

Brown

Kiyatkin

2008

Brain Research

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Intravenous (iv) cocaine mimics salient somato-sensory stimuli in their ability to induce rapid physiological effects, which appear to involve its action on peripherally located neural elements and fast neural transmission via somato-sensory pathways. To further clarify this mechanism, single-unit recording with fine glass electrodes was used in awake rats to examine responses of ventral tegmental area (VTA) neurons, both presumed dopamine (DA) and non-DA, to iv cocaine and tail-press, a typical somato-sensory stimulus. To exclude the contribution of DA mechanisms to the observed neuronal responses to sensory stimuli and cocaine, recordings were conducted during full DA receptor blockade (SCH23390+eticloptide).Iv cocaine (0.25 mg/kg delivered over 10 s) induces significant excitations of ~63% of long-spike (presumed DA) and ~70% of short-spike (presumed non-DA) VTA neurons. In both subgroups, neuronal excitations occurred with short latencies (4-8 s), peaked at 10-20 s (30-40% increase over baseline) and disappeared at 30-40 s after the injection onset. Most long-(67%) and short-spike (89%) VTA neurons also showed phasic responses to tail-press (5-s). All responsive long-spike cells were excited by tail-press; excitations were very rapid (peak at 1 s) and strong (100% rate increase over baseline) but brief (2-3 s). In contrast, both excitations (60%) and inhibitions (29%) were seen in short-spike cells. These responses were also rapid and transient, but excitations of short-spike units were more prolonged and sustained (10-15 s) than in long-spike cells.These data suggest that in awake animals iv cocaine, like somato-sensory stimuli, rapidly and transiently excites VTA neurons of different subtypes. Therefore, along with direct action on specific brain substrates, central effects of cocaine may occur via indirect mechanism, involving peripheral neural elements, visceral sensory nerves and rapid neural transmission. Via this mechanism, cocaine, like somato-sensory stimuli, can rapidly activate DA neurons and induce phasic DA release, creating the conditions for DA accumulation by a later occurring and prolonged direct inhibiting action on DA uptake. By providing a rapid neural signal and triggering transient neural activation, such a peripherally driven action might play a crucial role in the sensory effects of COC, thus contributing to learning and development of drug-taking behavior.

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Section: Sensory Responses Of Ls and Ss Vta Neuronssupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Sensory effects of intravenous cocaine on dopamine and non-dopamine ventral tegmental area neurons

Brown

Kiyatkin

2008

Brain Research

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“…2B, two distinct optical stimulation protocols were tested. Impulse train stimulation (16 pulses, 10-ms duration, 30 Hz, repeated every 2 s) was used to simulate a burst firing pattern, similar to that observed during normal wakefulness (33). In addition, periodic step stimulation (cycles of 5-ms pulses at 50 Hz for 60 s, followed by 30-s pauses with no stimulation) was used, which is similar to the electrical stimulation protocol used in our previous study in rats (34).…”

Section: Resultsmentioning

confidence: 99%

“…Impulse train stimulation (16 pulses, 10-ms duration, 30 Hz, repeated every 2 s) was used to simulate a burst firing pattern (33), and periodic step stimulation (cycles of 5-ms pulses at 50 Hz for 60 s, followed by 30-s pauses with no stimulation) was used to simulate the electrical stimulation protocol used in our previous rat study (34). The two stimulation protocols were tested on separate days, with at least 3 d of rest provided between experiments, in random order.…”

Section: Methodsmentioning

confidence: 99%

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

Taylor

Dort

Kenny

et al. 2016

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

211

179

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Dopamine (DA) promotes wakefulness, and DA transporter inhibitors such as dextroamphetamine and methylphenidate are effective for increasing arousal and inducing reanimation, or active emergence from general anesthesia. DA neurons in the ventral tegmental area (VTA) are involved in reward processing, motivation, emotion, reinforcement, and cognition, but their role in regulating wakefulness is less clear. The current study was performed to test the hypothesis that selective optogenetic activation of VTA DA neurons is sufficient to induce arousal from an unconscious, anesthetized state. Floxed-inverse (FLEX)-Channelrhodopsin2 (ChR2) expression was targeted to VTA DA neurons in DA transporter (DAT)-cre mice (ChR2+ group; n = 6). Optical VTA stimulation in ChR2+ mice during continuous, steady-state general anesthesia (CSSGA) with isoflurane produced behavioral and EEG evidence of arousal and restored the righting reflex in 6/6 mice. Pretreatment with the D1 receptor antagonist SCH-23390 before optical VTA stimulation inhibited the arousal responses and restoration of righting in 6/6 ChR2+ mice. In control DAT-cre mice, the VTA was targeted with a viral vector lacking the ChR2 gene (ChR2− group; n = 5). VTA optical stimulation in ChR2− mice did not restore righting or produce EEG changes during isoflurane CSSGA in 5/5 mice. These results provide compelling evidence that selective stimulation of VTA DA neurons is sufficient to induce the transition from an anesthetized, unconscious state to an awake state, suggesting critical involvement in behavioral arousal.anesthesia | ventral tegmental area | dopamine | optogenetics | arousal

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“…Although in vitro studies suggest that uptake inhibition is the primary action of COC (Heikkela et al 1975), after iv administration COC may affect monoamine release via indirect, sensory mechanisms before it reaches the brain. It is known that the activity of central neurons containing DA, norephinephrine and serotonin are modulated by sensory stimuli, producing in most cases phasic neuronal excitations (Aston-Jones and Bloom, 1981;Dahan et al, 2007;Heym et al, 1982;Steinfels et al, 1983). For example, most presumed DA VTA neurons recorded in awake rats change their activity rate or pattern (preferentially increase) following presentation of both simple sensory (light, sound) and aversive (tail-pinch and noxious tail-prick) stimuli, showing a tight correlation with stimuli-induced motor (EMG) and autonomic (arterial blood pressure) responses (Kiyatkin, 1988).…”

Section: Functional Implicationsmentioning

confidence: 99%

I.v. cocaine induces rapid, transient excitation of striatal neurons via its action on peripheral neural elements: Single-cell, iontophoretic study in awake and anesthetized rats

Kiyatkin

Brown

2007

Neuroscience

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Cocaine's (COC) direct interaction with the dopamine (DA) transporter is usually considered the most important action underlying the psychomotor stimulant and reinforcing effects of this drug. However, some physiological, behavioral and psycho-emotional effects of COC are very rapid and brief and they remain intact during DA receptor blockade, suggesting possible involvement of peripheral non-DA neural mechanisms.To assess this issue, single-unit recording with microiontophoresis was used to examine changes in impulse activity of dorsal and ventral striatal neurons to intravenous (iv) COC (0.25-0.5 mg/kg) in the same rats under two conditions: awake with dopamine (DA) receptor blockade and anesthetized with urethane. In the awake preparation ~70% striatal neurons showed rapid and transient (latencỹ 6 s, duration ~15 s) COC-induced excitations. These effects were stronger in ventral than dorsal striatum. During anesthesia, these phasic effects were fully blocked and COC slowly decreased neuronal discharge rate. COC-methiodide (COC-M), a derivative that cannot cross the blood-brain barrier, also caused phasic excitations in the awake, but not anesthetized condition. In contrast to regular COC, COC-M had no tonic effect on discharge rate in either preparation. Most striatal neurons that were phasically excited by both COC forms also showed short-latency excitations during tailtouch and tail-pinch in the awake preparation, an effect strongly attenuated during anesthesia. Finally, most striatal neurons that in awake conditions were phasically excited by somato-sensory stimuli and COC salts were also excited by iontophoretic glutamate (GLU). Although striatal neurons were sensitive to GLU in both preparations, the response magnitude at the same GLU current was higher in awake than anesthetized conditions. These data suggest that in awake animals iv COC, like somato-sensory stimuli, transiently excites striatal neurons via its action on peripheral neural elements and rapid neural transmission. While the nature of these neuronal elements needs to be clarified using other analytical techniques, they might involve voltage-gated K + and Na + channels, which have a high affinity for COC and are located on terminals of visceral sensory nerves that densely innervate peripheral vessels. Therefore, along with direct action on specific brain substrates, central excitatory effects of COC may occur via indirect action, involving afferents of visceral sensory nerves and rapid neural transmission. By providing a rapid sensory signal and triggering transient neural activation, such a peripherally triggered action might play a crucial role in the sensory effects of COC, thus contributing to learning and development of drug-taking behavior.* Correspondence should be addressed to Eugene A. Kiyatkin at the above address. Fax: (410) 550-5553; tel.: (410) 550-5551; e-mail: ekiyatki@intra.nida.nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our cus...

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Prominent Burst Firing of Dopaminergic Neurons in the Ventral Tegmental Area during Paradoxical Sleep

Cited by 255 publications

References 96 publications

Sensory effects of intravenous cocaine on dopamine and non-dopamine ventral tegmental area neurons

Sensory effects of intravenous cocaine on dopamine and non-dopamine ventral tegmental area neurons

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

I.v. cocaine induces rapid, transient excitation of striatal neurons via its action on peripheral neural elements: Single-cell, iontophoretic study in awake and anesthetized rats

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