Nucleus Accumbens Fast-Spiking Interneurons Constrain Impulsive Action

Pisansky, Marc T.; Lefevre, Emilia M.; Retzlaff, Cassandra L; Trieu, Brian H.; Leipold, David W.; Rothwell, Patrick E.

doi:10.1016/j.biopsych.2019.07.002

Cited by 59 publications

(37 citation statements)

References 78 publications

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“…Moreover, selection mechanisms are required to resolve any conflict between demands for these ensembles as they arise to ensure that incompatible behaviors do not occur at the same time animal (freeze v flight; approach v withdraw; initiate v terminate feeding). Selection mechanisms almost certainly exist in the complex, local inhibitory circuits of the Acb (Gerfen and Surmeier, 2011;Pisansky et al, 2019) and CeA (Ciocchi et al, 2010;Douglass et al, 2017), but as shown below, there is good evidence that they may also exist in the form of long-range circuits involving the paraventricular thalamus (PVT) and its interface with these local inhibitory circuits.…”

Section: Resultsmentioning

confidence: 99%

An arbiter model of motivational selection

McNally¹

2019

Preprint

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Although significant progress has been made in understanding how learning controls the operation of motivational systems, much less is known about how motivational systems control behavior to achieve motivational stability and resolve motivational conflict. Here we provide an overview of the basic characteristics of motivational conflict as well as historically influential approaches to understanding motivational stability and conflict. This is followed by an outline of an arbiter model of motivational stability and conflict that shares concepts with theories of perceptual decision making and executive function. This model uses a simple architecture to arbiter bistable transitions between motivational states and resolve any conflict between these states. A physiological instantiation of this model is described in paraventricular thalamus control of neuronal ensembles in the accumbens shell and extended amygdala. Finally, we consider applications of the arbiter model to disorders such as clinical anxiety and addictions.

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Section: Resultsmentioning

confidence: 99%

An arbiter model of motivational selection

McNally¹

2019

Preprint

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“…Additionally, the NAc core receives top-down glutamatergic inputs from several other brain regions, such as the ventral hippocampus or insula (48,49). It has been shown that fast-spiking interneurons in the NAc core have different levels of activity leading up to correct and premature responses in the 5-CSRTT, indicating that this area is active during the task (19). We also find that NAc neurons show a depressing response to vmPFC input, and that VMS-projecting neurons do show delay-dependent kinetics of population activity, even though signal amplitude was not significantly increased from baseline.…”

Section: Discussionmentioning

confidence: 99%

“…These circuits maintain activity during cognitive control tasks, and are thought to guide correct behavioral output by maintaining a representation of a task rule (13)(14)(15)(16)(17). Likewise, the dorsomedial and ventromedial striatum (DMS/VMS) have both been linked to inhibitory control and attention (18)(19)(20) and receive input from the dmPFC and vmPFC, respectively. Moreover, specific mPFC-DMS projections are linked to development of cognitive control and show ramping during preparatory attention (12,21), whereas mPFC-VMS projections are associated with anticipation and reward processing during cognitive control tasks (11,22,23).…”

Section: Introductionmentioning

confidence: 99%

Bi-directional command of cognitive control by distinct prefrontal cortical output neurons to thalamus and striatum

Kloet

Bruinsma

Terra

et al. 2020

Preprint

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The medial prefrontal cortex (mPFC) steers goal-directed actions and withholds inappropriate behavior. Dorsal and ventral mPFC (dmPFC/vmPFC) circuits have distinct roles in cognitive control, but underlying mechanisms are poorly understood. In this study, we provide anatomical, behavioral, and neurophysiological evidence for distinct roles of four distinct prefrontal projection populations in behavior. We used neuroanatomical tracing techniques, chemogenetics and fiber photometry in freely behaving rats, and in vitro electrophysiology to characterize dmPFC and vmPFC outputs to distinct thalamic and striatal subdomains and show that they have dissociable roles in cognitive control. We identify four spatially segregated projection neuron populations in the mPFC. Chemogenetic silencing shows that dmPFC and vmPFC projections to lateral and medial mediodorsal thalamus subregions oppositely regulate cognitive control. In addition, superficial and deep layer dmPFC neurons projecting to striatum and thalamus divergently regulate cognitive control. Using fiber photometry, we show that these projections distinctly encode behavior. Finally, we show that postsynaptic striatal and thalamic neurons differentially process synaptic inputs from dmPFC and vmPFC, highlighting mechanisms that potentially amplify distinct pathways underlying cognitive control of behavior. Collectively, we show that mPFC output circuits targeting anatomically and functionally distinct striatal and thalamic subregions encode bidirectional command of cognitive control.

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“…Whole-cell voltage-clamp recordings from nucleus accumbens MSNs in acute brain slices were performed as previously described [32]. Miniature inhibitory post-synaptic currents (mIPSCs) were recorded at a holding potential of 0 mV and pharmacologically isolated using D-APV (50 mM), NBQX (10 mM), and tetrodotoxin (0.5 µM).…”

Section: Electrophysiologymentioning

confidence: 99%

Mu Opioid Receptor Gene Dosage Influences Reciprocal Social Behaviors and Nucleus Accumbens Microcircuitry

Toddes

Lefevre

Brandner

et al. 2020

Preprint

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The mu opioid receptor regulates reward derived from both drug use and natural experiences, including social interaction. Homozygous genetic knockout of the mu opioid receptor (Oprm1-/-) causes social deficits in mice, whereas partial dysregulation of mu opioid signaling has been documented in several human neuropsychiatric disorders. Here, we investigated the social behavior of male and female mice with heterozygous genetic knockout of the mu opioid receptor (Oprm1+/-), modeling partial reduction of mu opioid signaling. Reciprocal social interaction and social conditioned place preference were diminished in Oprm1+/- and Oprm1-/- mutants of both sexes. Interaction with Oprm1 mutants also altered the social behavior of genotypical test partners. We corroborated this latter result using a social preference task, in which genotypical mice preferred interactions with another typical mouse over Oprm1 mutants. We also analyzed inhibitory synapses in the nucleus accumbens, a key brain region for mu opioid regulation of social behavior, using methods that differentiate between medium spiny neurons (MSNs) expressing the D1 or D2 dopamine receptor. Inhibitory synaptic transmission was increased in D2-MSNs of male mutants, but not female mutants, while the density of inhibitory synaptic puncta at the cell body of D2-MSNs was increased in both male and female mutants. These changes in nucleus accumbens microcircuitry were more robust in Oprm1+/- mutants than Oprm1-/- mutants, demonstrating that partial reductions of mu opioid signaling can have large effects on brain function and behavior. Our results support a role for partial dysregulation of mu opioid signaling in social deficits associated with neuropsychiatric conditions.

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Nucleus Accumbens Fast-Spiking Interneurons Constrain Impulsive Action

Cited by 59 publications

References 78 publications

An arbiter model of motivational selection

An arbiter model of motivational selection

Bi-directional command of cognitive control by distinct prefrontal cortical output neurons to thalamus and striatum

Mu Opioid Receptor Gene Dosage Influences Reciprocal Social Behaviors and Nucleus Accumbens Microcircuitry

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