Uniform Inhibition of Dopamine Neurons in the Ventral Tegmental Area by Aversive Stimuli

Ungless, Mark A.; Magill, Peter J.; Bolam, J. Paul

doi:10.1126/science.1093360

Cited by 684 publications

(650 citation statements)

References 25 publications

(31 reference statements)

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“…Indeed, whereas 5-HT inhibits DA release (Kapur & Remington, 1996; potentially via 5-HT receptors in DA cells, Nocjar, Roth, & Pehek, 2002), there is no reciprocal relationship for DA onto 5-HT (Adell & Artigas, 1999). Finally, although DA dips have been repeatedly observed when outcomes are worse than expected (e.g., Bayer & Glimcher, 2005;Hollerman & Schultz, 1998;Morris, Arkadir, Nevet, Vaadia, & Bergman, 2004;Satoh et al, 2003;Schultz, 1999;Ungless, Magill, & Bolam, 2004), the predicted phasic increase in 5-HT during these negative prediction errors has yet to be observed (see Daw et al, 2002), and if it is observed, it is unclear how it would preferentially bias no-go learning in the BG.…”

Section: Model Limitations and Further Neurobiological Considerationsmentioning

confidence: 99%

Anatomy of a decision: Striato-orbitofrontal interactions in reinforcement learning, decision making, and reversal.

Frank¹,

Claus²

2006

Psychological Review

523

505

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The authors explore the division of labor between the basal ganglia-dopamine (BG-DA) system and the orbitofrontal cortex (OFC) in decision making. They show that a primitive neural network model of the BG-DA system slowly learns to make decisions on the basis of the relative probability of rewards but is not as sensitive to (a) recency or (b) the value of specific rewards. An augmented model that explores BG-OFC interactions is more successful at estimating the true expected value of decisions and is faster at switching behavior when reinforcement contingencies change. In the augmented model, OFC areas exert top-down control on the BG and premotor areas by representing reinforcement magnitudes in working memory. The model successfully captures patterns of behavior resulting from OFC damage in decision making, reversal learning, and devaluation paradigms and makes additional predictions for the underlying source of these deficits.Keywords: decision making, neural network, basal ganglia, orbitofrontal cortex, reinforcement learning What enables humans to make choices that lead to long-term gains, even when having to incur short-term losses? Such decisionmaking skills depend on the processes of action selection (choosing between one of several possible responses) and reinforcement learning (modifying the likelihood of selecting a given response on the basis of experienced consequences). Although all mammals can learn to associate their actions with consequences, humans are particularly advanced in their ability to flexibly modify the relative reinforcement values of alternative choices to select the most adaptive behavior in a particular behavioral, spatial, and temporal context.The behavioral and cognitive neurosciences have identified two neural systems that are involved in such adaptive behavior. On the one hand, the basal ganglia (BG) and the neuromodulator dopamine (DA) are thought to participate in both action selection and reinforcement learning

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Section: Model Limitations and Further Neurobiological Considerationsmentioning

confidence: 99%

Anatomy of a decision: Striato-orbitofrontal interactions in reinforcement learning, decision making, and reversal.

Frank¹,

Claus²

2006

Psychological Review

523

505

View full text Add to dashboard Cite

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“…Presumed dopamine neurons were found 7.5-8.5 mm from the brain surface and were recognized by their characteristic triphasic action potential waveform of more than 2.0 ms duration, basal firing rates of 1-10 Hz, and frequent occurrence of burst firing (Wang, 1981). Moreover, the 'Ungless-filter', consisting of tail-or toe-pinch, was applied and only cells that responded with a transient inhibition of firing were included in the study (Ungless et al, 2004). Extracellular electrical activity was amplified, filtered (band pass 0.3-3 kHz), discriminated, and monitored on an oscilloscope (TDS 310, Tektronix, Beaverton, OR) and an audiomonitor (Grass, AM8B/C, West Warwick, RI).…”

Section: Extracellular Single Cell Recording Of Dopaminergic Neurons mentioning

confidence: 99%

Galantamine Enhances Dopaminergic Neurotransmission In Vivo Via Allosteric Potentiation of Nicotinic Acetylcholine Receptors

Schilström

Ivanov

Wiker

et al. 2006

Neuropsychopharmacol

115

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Clinical studies suggest that adjunct galantamine may improve negative and cognitive symptoms in schizophrenia. These symptoms may be related to impaired dopaminergic function in the prefrontal cortex. Indeed, galantamine has been shown to increase dopamine release in vitro. Galantamine is an allosteric modulator of nicotinic acetylcholine receptors (nAChRs) and, at higher doses, an acetylcholine esterase (AChE) inhibitor. We have previously shown that nicotine, through stimulation of nAChRs in the ventral tegmental area (VTA), activates midbrain dopamine neurons and, hence, potentiation of these receptors could be an additional mechanism by which galantamine can activate dopaminergic pathways. Therefore, the effects of galantamine (0.01-1.0 mg/kg s.c.) on dopamine cell firing were tested in anaesthetized rats. Already at a low dose, unlikely to result in significant AchE inhibition, galantamine increased firing activity of dopaminergic cells in the VTA. The effect of galantamine was prevented by the nAChR antagonist mecamylamine (1.0 mg/kg s.c.), but not the muscarinic receptor antagonist scopolamine (0.1 mg/kg s.c.), and it was not mimicked by the selective AChE inhibitor donepezil (1.0 mg/kg s.c.). Our data thus indicate that galantamine increases dopaminergic activity through allosteric potentiation of nAChRs. Galantamine's effect was also prevented by the a7 nAChR antagonist methyllycaconitine (6.0 mg/kg i.p.) as well as the N-methyl-Daspartate antagonist CGP39551 (2.5 mg/kg s.c.), indicating a mechanism involving presynaptic facilitation of glutamate release. In parallel microdialysis experiments, galantamine was found to increase extracellular levels of dopamine in the medial prefrontal cortex. These results may have bearing on the enhancement of negative and cognitive symptoms in schizophrenia.

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“…1), where the fast-firing mesocortical cells are preferentially located (Chiodo et al 1984). However, several recent studies questioned the traditional criteria of indirect DA cell identification as less reliable and absolute than was originally thought (Ungless et al, 2004;Margolis et al, 2006). Using Neurobiotin staining with subsequent histochemical identification of the recorded cells in anesthetized conditions, Ungless et al (2004) showed that not all VTA cells with long, triphasic cells (10/18) are DA-containing, although they found that spike duration is relatively longer in identified DA cells compared to non-DA neurons.…”

Section: Vta Cell Heterogeneity and The Issue Of Neuronal Phenotypementioning

confidence: 99%

“…However, several recent studies questioned the traditional criteria of indirect DA cell identification as less reliable and absolute than was originally thought (Ungless et al, 2004;Margolis et al, 2006). Using Neurobiotin staining with subsequent histochemical identification of the recorded cells in anesthetized conditions, Ungless et al (2004) showed that not all VTA cells with long, triphasic cells (10/18) are DA-containing, although they found that spike duration is relatively longer in identified DA cells compared to non-DA neurons. Therefore, conservatively we can assume that some LS VTA cells recorded in this study could be non-DA cells and such a possibility has been suggested in our previous work (Kiyatkin and Rebec, 1998).…”

Section: Vta Cell Heterogeneity and The Issue Of Neuronal Phenotypementioning

confidence: 99%

“…It appears that this response is typical to the awake conditions when sensory effects and activation mechanisms are intact and functional; somatosensory-evoked discharges typical to most striatal neurons were greatly eliminated during general anesthesia (see Kiyatkin and Brown, 2007;West, 1996). During general anesthesia presumed DA cells generally show no changes in activity following mild sensory stimulation (Coizet et al, 2006;Schultz and Romo, 1987;Tsai et al, 1980) but are both inhibited and activated by very strong, "noxious" stimuli (Chiodo et al, 1980;Coizet et al, 2006;Hommer and Bunney, 1980;Maeda and Mogenson, 1982;Schultz and Romo, 1987;Ungless et al, 2004). Although the ratio of opposite responses widely varied, the excitations were usually much stronger than inhibitions in terms of magnitude (Chiodo et al, 1979;Mantz et al, 1989) and they were predominant in mesocortical DA cells (Mantz et al, 1989).…”

Section: Sensory Responses Of Ls and Ss Vta Neuronsmentioning

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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Uniform Inhibition of Dopamine Neurons in the Ventral Tegmental Area by Aversive Stimuli

Cited by 684 publications

References 25 publications

Anatomy of a decision: Striato-orbitofrontal interactions in reinforcement learning, decision making, and reversal.

Anatomy of a decision: Striato-orbitofrontal interactions in reinforcement learning, decision making, and reversal.

Galantamine Enhances Dopaminergic Neurotransmission In Vivo Via Allosteric Potentiation of Nicotinic Acetylcholine Receptors

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

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