A Neural Circuit Mechanism for Encoding Aversive Stimuli in the Mesolimbic Dopamine System

Jong, Johannes de; Afjei, Seyedeh Atiyeh; Dorocic, Iskra Pollak; Peck, James R.; Liu, Christine; Kim, Christina K.; Tian, Lin; Deisseroth, Karl; Lammel, Stephan

doi:10.1016/j.neuron.2018.11.005

Cited by 381 publications

(426 citation statements)

References 80 publications

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“…Consistent with known connectivity (de Jong et al, 2019;Lammel et al, 2011;Lammel et al, 2013;Yang et al, 2018), the Region RDM ( Figure 4B) showed that across self-administration to relapse, the signatures of lVTA and AcbC as well as mVTA and AcbShM were highly similar. Surprisingly, the signatures of the three Acb regions were highly dissimilar.…”

Section: Identifying and Comparing Mesolimbic Dopamine Signaturessupporting

confidence: 72%

“…However, the mesolimbic dopamine system has a complex architecture. VTA dopamine neurons form distinct channels linked to differences in behavioral and motivational function (Cohen et al, 2012;de Jong et al, 2019;Heymann et al, 2019;Lammel et al, 2008;Lammel et al, 2011;Lammel et al, 2013;Saunders et al, 2018;Tian et al, 2016;Watabe-Uchida et al, 2012). In turn, there are distinct profiles of dopamine release across compartments of the ventral striatum giving rise to different functions (de Jong et al, 2019;Mohebi et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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The mesolimbic dopamine signatures of relapse to alcohol-seeking

Liu

Bressel

Yau

et al. 2020

Preprint

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The mesolimbic dopamine system comprises distinct compartments supporting different functions in learning and motivation. Less well understood is how complex addiction-related behaviors emerge from activity patterns across these compartments. Here we show how different forms of relapse to alcohol-seeking are assembled from activity across the ventral tegmental area and the nucleus accumbens. Using gCaMP and dLight fibre photometry, we show that self-administration and two forms of relapse (renewal/context-induced reinstatement and reacquisition) are associated with recruitment across the mesolimbic dopamine system. Using a variety of interventions, we show that this activity is causal to both forms of relapse. Finally, we use dissimilarity matrices to identify mesolimbic dopamine signatures of self-administration, extinction, and relapse. We show that signatures of relapse can be identified from heterogeneous activity profiles across the mesolimbic dopamine system and that these signatures differ for different forms of relapse.

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Section: Identifying and Comparing Mesolimbic Dopamine Signaturessupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

The mesolimbic dopamine signatures of relapse to alcohol-seeking

Liu

Bressel

Yau

et al. 2020

Preprint

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“…Additionally, in the PFC, decreased GABA A ‐stimulated chloride influx was evident in a membrane preparation from 24‐h isolated rats along with reduced benzodiazepine binding, indicating a decrease in cortical GABA A expression and/or function. Given the functional diversity of dopamine input to striatal subregions and dopamine's divergent effects on cortical projector populations, further work is necessary to elucidate precisely how these rapid isolation‐induced changes to dopamine neurotransmission influence downstream activity.…”

Section: Homeostatic Response To Social Deficit: Engaging Social Motimentioning

confidence: 99%

Neural mechanisms of social homeostasis

Matthews

Tye

2019

Annals of the New York Academy of Sciences

126

102

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Social connections are vital to survival throughout the animal kingdom and are dynamic across the life span. There are debilitating consequences of social isolation and loneliness, and social support is increasingly a primary consideration in health care, disease prevention, and recovery. Considering social connection as an “innate need,” it is hypothesized that evolutionarily conserved neural systems underlie the maintenance of social connections: alerting the individual to their absence and coordinating effector mechanisms to restore social contact. This is reminiscent of a homeostatic system designed to maintain social connection. Here, we explore the identity of neural systems regulating “social homeostasis.” We review findings from rodent studies evaluating the rapid response to social deficit (in the form of acute social isolation) and propose that parallel, overlapping circuits are engaged to adapt to the vulnerabilities of isolation and restore social connection. By considering the neural systems regulating other homeostatic needs, such as energy and fluid balance, we discuss the potential attributes of social homeostatic circuitry. We reason that uncovering the identity of these circuits/mechanisms will facilitate our understanding of how loneliness perpetuates long‐term disease states, which we speculate may result from sustained recruitment of social homeostatic circuits.

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“…Finally, our study gives further support to the idea that mesolimbic DA neurons projecting to medial versus lateral shell of accumbens constitute two parallel pathways. Recent studies highlighted the differential functional roles of these DA projections, as well as their distinct circuit affiliations (de Jong et al, 2019;Lammel et al, 2012;Yang et al, 2018). Our frequency data suggest that these two DA projections operate at different baseline excitation/inhibition (E/I) setpoints in vivo.…”

Section: Discussionmentioning

confidence: 70%

“…The functional properties and the emerging diversity of the midbrain dopamine (DA) system have been extensively studied across many different biological scales (Schultz, 2015;Watabe-Uchida et al, 2017). These differences range from the single-cell level, including diverging gene expression profiles (Kramer et al, 2018;Nichterwitz et al, 2016;Poulin et al, 2018;Saunders et al, 2018a;Tiklova et al, 2019), cellular and biophysical properties Lammel et al, 2008;Tarfa et al, 2017), as well as neurotransmitter co-release (Chuhma et al, 2018;Kim et al, 2015b;Tritsch et al, 2012;Zhang et al, 2015), up to different neural circuit affiliations (Beier et al, 2019;Beier et al, 2015;Lammel et al, 2012;Lerner et al, 2015;Menegas et al, 2015;Ogawa et al, 2014;Tian et al, 2016;Watabe-Uchida et al, 2012) and selective task engagement of DA subpopulations in awake behaving rodents (Dautan et al, 2016;de Jong et al, 2019;Duvarci et al, 2018;Gunaydin et al, 2014;Howe and Dombeck, 2016;Keiflin et al, 2019;Lammel et al, 2012;Matthews et al, 2016;Menegas et al, 2018;Menegas et al, 2017;Parker et al, 2016;Patriarchi et al, 2018;Saunders et al, 2018b;Vander Weele et al, 2018;Yang et al, 2018) and non-human primates …”

Section: Introductionmentioning

confidence: 99%

In vivo functional diversity of midbrain dopamine neurons within identified axonal projections

Farassat

Costa

Albert

et al. 2019

Preprint

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The functional diversity of midbrain dopamine (DA) neurons ranges across multiple scales, from differences in intrinsic properties and synaptic connectivity to selective task engagement in behaving animals. Distinct in vitro biophysical features of DA neurons have been associated with different axonal projection targets. However, it is unknown how this translates to different firing patterns of projection-defined DA subpopulations in the intact brain. We combined retrograde tracing with single-unit recording and juxtacellular labelling in mouse brain to create the first single cellresolved in vivo functional topography of the midbrain DA system. We identified surprising differences in burst firing among those DA neurons projecting to dorsolateral striatum, which were organized along the medio-lateral substantia nigra (SN) axis. Furthermore, burst properties also differentiated DA neurons in the medial SN that projected either to dorsal or ventral striatum. In contrast, DA neurons projecting to lateral shell of nucleus accumbens displayed identical firing properties, irrespective of whether they were located in the SN or ventral tegmental area (VTA), thus breaching classical anatomical boundaries. Finally, we found robust differences in mean firing rates and pause durations among VTA DA neurons projecting to either lateral or medial shell of nucleus accumbens. Together, our data set establishes a high-resolution functional landscape of midbrain DA neurons, which will facilitate the identification of selective functions and pathophysiological changes within the midbrain DA system.

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A Neural Circuit Mechanism for Encoding Aversive Stimuli in the Mesolimbic Dopamine System

Cited by 381 publications

References 80 publications

The mesolimbic dopamine signatures of relapse to alcohol-seeking

The mesolimbic dopamine signatures of relapse to alcohol-seeking

Neural mechanisms of social homeostasis

In vivo functional diversity of midbrain dopamine neurons within identified axonal projections

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