Coordination of Brain-Wide Activity Dynamics by Dopaminergic Neurons

Decot, Heather; Namboodiri, Vijay Mohan K.; Gao, Wei; McHenry, Jenna A.; Jennings, Joshua H.; Lee, Sung Ho; Kantak, Pranish A.; Kao, Yu Chieh Jill; Das, Manasmita; Witten, Ilana B.; Deisseroth, Karl; Shih, Yen‐Yu Ian; Stuber, Garret D.

doi:10.1038/npp.2016.151

Cited by 62 publications

(76 citation statements)

References 77 publications

(95 reference statements)

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“…Similarly, recent fMRI studies employing optogenetics to stimulate midbrain dopamine neuron activity reported CBV and BOLD signal increases in rat striatum (Decot et al 2016; Ferenczi et al 2016; Lohani et al 2016). …”

Section: Discussionmentioning

confidence: 82%

The role of beta-arrestin2 in shaping fMRI BOLD responses to dopaminergic stimulation

Sahlholm

Ielacqua

et al. 2017

Psychopharmacology

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RationaleThe dopamine D2 receptor (D2R) couples to inhibitory Gi/o proteins and is targeted by antipsychotic and antiparkinsonian drugs. Beta-arrestin2 binds to the intracellular regions of the agonist-occupied D2R to terminate G protein activation and promote internalization, but also to initiate downstream signaling cascades which have been implicated in psychosis. Functional magnetic resonance imaging (fMRI) has proven valuable for measuring dopamine receptor-mediated changes in neuronal activity, and might enable beta-arrestin2 function to be studied in vivo.ObjectivesThe present study examined fMRI blood oxygenation level dependent (BOLD) signal changes elicited by a dopamine agonist in wild-type (WT) and beta-arrestin2 knockout (KO) mice, to investigate whether genetic deletion of beta-arrestin2 prolongs or otherwise modifies D2R-dependent responses.MethodsfMRI BOLD data were acquired on a 9.4 T system. During scans, animals received 0.2 mg/kg apomorphine, i.v. In a subset of experiments, animals were pretreated with 2 mg/kg of the D2R antagonist, eticlopride.ResultsFollowing apomorphine administration, BOLD signal decreases were observed in caudate/putamen of WT and KO animals. The time course of response decay in caudate/putamen was significantly slower in KO vs. WT animals. In cingulate cortex, an initial BOLD signal decrease was followed by a positive response component in WT but not in KO animals. Eticlopride pretreatment significantly reduced apomorphine-induced BOLD signal changes.ConclusionsThe prolonged striatal response decay rates in KO animals might reflect impaired D2R desensitization, consistent with the known function of beta-arrestin2. Furthermore, the apomorphine-induced positive response component in cingulate cortex may depend on beta-arrestin2 signaling downstream of D2R.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-017-4609-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 82%

The role of beta-arrestin2 in shaping fMRI BOLD responses to dopaminergic stimulation

Sahlholm

Ielacqua

et al. 2017

Psychopharmacology

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“…This serves one of two functions: (1) To increase the activity of downstream neurons in driving behavior and (2) Increasing the strength of these specific inputs via changes in plasticity. This can occur in all of the projection regions of the VTA, has been seen in the PFC, NAc, and amygdala, and gives further support that these initial dopaminergic changes can induce widespread circuit dysfunction in a range of circuits across the brain to drive maladaptive behaviors (Decot et al, 2017). …”

Section: The Neural Circuits Controlling Motivated Behaviors and Thmentioning

confidence: 80%

“…This is a critical consideration as these types of changes prevent further learning-induced plasticity and can drive compulsive behaviors. However, this is even more important in the context of other glutamatergic circuits across the brain, where changes in striatal circuits lead to more widespread alterations in other brain regions (Baler and Volkow, 2006; Decot et al, 2017; Kalivas and Volkow, 2005; Koob and Volkow, 2016; Moeller et al, 2010). …”

Section: The Neural Circuits Controlling Motivated Behaviors and Thmentioning

confidence: 99%

Cross-talk between the epigenome and neural circuits in drug addiction

Mews

Calipari

2017

Progress in Brain Research

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Drug addiction is a behavioral disorder characterized by dysregulated learning about drugs and associated cues that result in compulsive drug seeking and relapse. Learning about drug rewards and predictive cues is a complex process controlled by a computational network of neural connections interacting with transcriptional and molecular mechanisms within each cell to precisely guide behavior. The interplay between rapid, temporally specific neuronal activation, and longer-term changes in transcription is of critical importance in the expression of appropriate, or in the case of drug addiction, inappropriate behaviors. Thus, these factors and their interactions must be considered together, especially in the context of treatment. Understanding the complex interplay between epigenetic gene regulation and circuit connectivity will allow us to formulate novel therapies to normalize maladaptive reward behaviors, with a goal of modulating addictive behaviors, while leaving natural reward-associated behavior unaffected.

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“…Given that the electrodes are estimated to be sensitive to changes in signal over approximately a 400μm sphere around the electrode [53,54], it is plausible that the signals we recorded here could have been influenced by RPE-like patterns of dopamine release [55]. Several recent papers have shown that optogenetic stimulation of dopamine neurons can have widespread influence on forebrain BOLD signals [56][57][58]. However, direct evidence for this link is currently lacking, and a recent study comparing patterns of BOLD signals with dopamine release in humans found indications of uncoupling between the measures [59].…”

Section: Discussionmentioning

confidence: 96%

Amphetamine disrupts haemodynamic correlates of prediction errors in nucleus accumbens and orbitofrontal cortex

Werlen

Shin

Gastambide

et al. 2019

Preprint

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In an uncertain world, the ability to predict and update the relationships between environmental cues and outcomes is a fundamental element of adaptive behaviour. This type of learning is typically thought to depend on prediction error, the difference between expected and experienced events, and in the reward domain this has been closely linked to mesolimbic dopamine. There is also increasing behavioural and neuroimaging evidence that disruption to this process may be a cross-diagnostic feature of several neuropsychiatric and neurological disorders in which dopamine is dysregulated. However, the precise relationship between haemodynamic measures, dopamine and reward-guided learning remains unclear.To help address this issue, we used a translational technique, oxygen amperometry, to record haemodynamic signals in the nucleus accumbens (NAc) and orbitofrontal cortex (OFC) while freely-moving rats performed a probabilistic Pavlovian learning task. Using a model-based analysis approach to account for individual variations in learning, we found that the oxygen signal in the NAc correlated with a reward prediction error, whereas in the OFC it correlated with an unsigned prediction error or salience signal. Furthermore, an acute dose of amphetamine, creating a hyperdopaminergic state, disrupted rats' ability to discriminate between cues associated with either a high or a low probability of reward and concomitantly corrupted prediction error signalling. These results demonstrate parallel but distinct prediction error signals in NAc and OFC during learning, both of which are affected by psychostimulant administration. Furthermore, they establish the viability of tracking and manipulating haemodynamic signatures of reward-guided learning observed in human fMRI studies using a proxy signal for BOLD in a freely behaving rodent.

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Coordination of Brain-Wide Activity Dynamics by Dopaminergic Neurons

Cited by 62 publications

References 77 publications

The role of beta-arrestin2 in shaping fMRI BOLD responses to dopaminergic stimulation

The role of beta-arrestin2 in shaping fMRI BOLD responses to dopaminergic stimulation

Cross-talk between the epigenome and neural circuits in drug addiction

Amphetamine disrupts haemodynamic correlates of prediction errors in nucleus accumbens and orbitofrontal cortex

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