Coincident but Distinct Messages of Midbrain Dopamine and Striatal Tonically Active Neurons

Morris, Genela; Arkadir, David; Nevet, Alon; Vaadia, Eilon; Bergman, Hagai

doi:10.1016/j.neuron.2004.06.012

Cited by 490 publications

(620 citation statements)

References 63 publications

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“…This feature distinguishes the TANs from mesostriatal DANs, which are equally responsive to both rewards and their associated cues. In addition, TANs do not show a differential response based on reward probability whereas striatal DA activation reflects a mismatch between expectation and outcome (Morris et al, 2004). (These findings are best described for cholinergic interneurons in the dorsal striatum.)…”

Section: Mesostriatal Cholinergic Neuronsmentioning

confidence: 91%

The Role of Acetylcholine in Cocaine Addiction

Williams

Adinoff²

2007

Neuropsychopharmacol

160

138

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Central nervous system cholinergic neurons arise from several discrete sources, project to multiple brain regions, and exert specific effects on reward, learning, and memory. These processes are critical for the development and persistence of addictive disorders. Although other neurotransmitters, including dopamine, glutamate, and serotonin, have been the primary focus of drug research to date, a growing preclinical literature reveals a critical role of acetylcholine (ACh) in the experience and progression of drug use. This review will present and integrate the findings regarding the role of ACh in drug dependence, with a primary focus on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine administration produces neuroadaptive changes in the striatum. ACh is further involved in the acquisition of conditional associations that underlie cocaine self-administration and context-dependent sensitization, the acquisition of associations in conditioned learning, and drug procurement through its effects on arousal and attention. Long-term cocaine use may induce neuronal alterations in the brain that affect the ACh system and impair executive function, possibly contributing to the disruptions in decision making that characterize this population. These primarily preclinical studies suggest that ACh exerts a myriad of effects on the addictive process and that persistent changes to the ACh system following chronic drug use may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a potential target for pharmacological treatment interventions in cocaine-addicted subjects. However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of the striatal cholinergic interneurons suggest that a precise target of cholinergic manipulation will be required to impact substance use in the clinical population.

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Section: Mesostriatal Cholinergic Neuronsmentioning

confidence: 91%

The Role of Acetylcholine in Cocaine Addiction

Williams

Adinoff²

2007

Neuropsychopharmacol

160

138

View full text Add to dashboard Cite

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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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“…While these regional differences primarily identify a nAChR that offers a potential means for differentially modifying ACh-DA and nicotine-DA interactions in ventral vs dorsal striatum, it is possible that these data might also impact on how synchronized pauses in cholinergic neurons that occur in response to reward-related cues (Morris et al, 2004) govern DA function (Cragg, 2006). Differences (albeit currently unresolved) in affinity for ACh of each receptor type might have some impact on the efficacy or speed (and therefore time window) with which a fall and rise in striatal ACh tone at nAChRs would be detected and impact on striatal DA release following a synchronized pause in ACh neurons.…”

Section: Dominant Role For A6 Subunit In Nac But Not Cpumentioning

confidence: 99%

α6-Containing Nicotinic Acetylcholine Receptors Dominate the Nicotine Control of Dopamine Neurotransmission in Nucleus Accumbens

Exley

Clements

Hartung

et al. 2007

Neuropsychopharmacol

227

265

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Modulation of striatal dopamine (DA) neurotransmission plays a fundamental role in the reinforcing and ultimately addictive effects of nicotine. Nicotine, by desensitizing b2 subunit-containing (b2*) nicotinic acetylcholine receptors (nAChRs) on striatal DA axons, significantly enhances how DA is released by reward-related burst activity compared to nonreward-related tonic activity. This action provides a synaptic mechanism for nicotine to facilitate the DA-dependent reinforcement. The subfamily of b2*-nAChRs responsible for these potent synaptic effects could offer a molecular target for therapeutic strategies in nicotine addiction. We explored the role of a6b2*-nAChRs in the nucleus accumbens (NAc) and caudate-putamen (CPu) by observing action potential-dependent DA release from synapses in real-time using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in mouse striatal slices. The a6-specific antagonist a-conotoxin-MII suppressed DA release evoked by single and low-frequency action potentials and concurrently enhanced release by high-frequency bursts in a manner similar to the b2*-selective antagonist dihydro-b-erythroidine (DHbE) in NAc, but less so in CPu. The greater role for a6*-nAChRs in NAc was not due to any confounding regional difference in ACh tone since elevated ACh levels (after the acetylcholinesterase inhibitor ambenonium) had similar outcomes in NAc and CPu. Rather, there appear to be underlying differences in nAChR subtype function in NAc and CPu. In summary, we reveal that a6b2*-nAChRs dominate the effects of nicotine on DA release in NAc, whereas in CPu their role is minor alongside other b2*-nAChRs (eg a4*), These data offer new insights to suggest striatal a6*-nAChRs as a molecular target for a therapeutic strategy for nicotine addiction.

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Coincident but Distinct Messages of Midbrain Dopamine and Striatal Tonically Active Neurons

Cited by 490 publications

References 63 publications

The Role of Acetylcholine in Cocaine Addiction

The Role of Acetylcholine in Cocaine Addiction

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

α6-Containing Nicotinic Acetylcholine Receptors Dominate the Nicotine Control of Dopamine Neurotransmission in Nucleus Accumbens

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