Prelimbic and infralimbic cortical inactivations attenuate contextually driven discriminative responding for reward

Riaz, Sadia; Puveendrakumaran, Pugaliya; Khan, Dinat; Yoon, Sharon; Hamel, Laurie; Ito, Rutsuko

doi:10.1038/s41598-019-40532-7

Cited by 37 publications

(24 citation statements)

References 66 publications

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“…This finding aligns with other reports implicating the PL and GABABR-dependent signaling in locomotor sensitization. For example, PL lesions blocked the induction and expression of cocaine-induced locomotor sensitization (17)(18)(19), and baclofen infusion into the mPFC blocked acute cocaine-induced locomotion and induction of locomotor sensitization without affecting basal activity (72,73). Collectively, these lines of evidence suggest that the cocaine-induced suppression of GIRK-dependent signaling in PL pyramidal neurons contributes to locomotor sensitization.…”

Section: Discussionmentioning

confidence: 92%

Divergent behavioral consequences of manipulations enhancing pyramidal neuron excitability in the prelimbic cortex

Rose

Velasco

et al. 2020

Preprint

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BackgroundDrug-induced neuroadaptations in the prefrontal cortex are thought to underlie impaired executive functions that reinforce addictive behaviors. Repeated cocaine exposure increased layer 5/6 pyramidal neuron excitability in the mouse prelimbic cortex (PL), an adaptation attributable to a suppression of G protein-gated inwardly rectifying K + (GIRK/Kir3) channel activity. GIRK channel suppression in the PL of drug-naïve mice enhanced the motor-stimulatory effect of cocaine. The impact of cocaine on PL GABA neurons, key pyramidal neuron regulators, and the behavioral relevance of increased PL pyramidal neuron excitability, remain unclear. MethodsThe effect of repeated cocaine on mouse layer 5/6 PL GABA neurons was assessed using slice electrophysiology. Adaptations enhancing PL pyramidal neuron excitability were modeled in drug-naïve mice using persistent viral Cre ablation and acute chemogenetic approaches. The impact of these manipulations on PL-dependent behavior was assessed in motor activity and trace fear conditioning tests. ResultsRepeated cocaine treatment did not impact GIRK channel activity in, or excitability of, layer 5/6 PL GABA neurons. GIRK channel ablation in PL pyramidal neurons enhanced the motor-stimulatory effect of cocaine but did not impact baseline activity or fear learning. In contrast, direct or indirect chemogenetic activation of PL pyramidal neurons increased baseline and cocaine-induced motor activity and disrupted fear learning. These effects were mirrored by chemogenetic activation of PL pyramidal neurons projecting to the ventral tegmental area. ConclusionsManipulations enhancing the excitability of PL pyramidal neurons, including those projecting to the VTA, recapitulate behavioral hallmarks of repeated cocaine exposure.

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Section: Discussionmentioning

confidence: 92%

Divergent behavioral consequences of manipulations enhancing pyramidal neuron excitability in the prelimbic cortex

Rose

Velasco

et al. 2020

Preprint

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“…Our finding that coordinated PL reorganization anticipates change in behavior toward extinction lends further credence to this hypothesis. In fact, ample evidence shows that in rat prefrontal cortex, particularly its prelimbic subregion, neural population dynamics is reshaped prior to rule and reversal learning of appetitive reward-seeking strategies (Durstewitz et al, 2010;Karlsson et al, 2012;Powell and Redish, 2016;Rich and Shapiro, 2009). In light of those studies, our results may suggest a causal link between PL coordination and strategy switching, irrespective of the particular mode of learning, i.e.…”

Section: Discussionmentioning

confidence: 99%

“…The rodent prelimbic mPFC (PL), together with the infralimbic mPFC (IL), is implicated in extinguishing reward-seeking behavior (Chen et al, 2013;Jonkman et al, 2009;Moorman and Aston-Jones, 2015;Riaz et al, 2019;Sharpe et al, 2019). Both pharmacological inactivation of PL and optogenetic stimulation of its inhibitory network during the presentation of conditioned stimuli facilitate extinction (Caballero et al, 2019;Sparta et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…While such manipulations highlight the role of mPFC in extinction of reward-seeking responses, the neural dynamics driving extinction is largely unknown. At the cellular level, acquisition of new behavioral strategies is associated with changes in PL and IL activity, with the PL predicting and the IL following the acquisition of the new contingency (Rich and Shapiro, 2009). Furthermore, sudden transitions in rodent mPFC activity signal rapid behavioral shifts during rule learning (Durstewitz et al, 2010) and mark the onset of the exploratory phase following changes in cued reward probabilities (Karlsson et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Coordinated prefrontal state transition leads extinction of reward-seeking behaviors

Russo

Spanagel

et al. 2020

Preprint

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Extinction learning suppresses conditioned reward responses and is thus fundamental to adapt to changing environmental demands and to control excessive reward seeking. The medial prefrontal cortex (mPFC) monitors and controls conditioned reward responses. Using in vivo multiple single-unit recordings of mPFC we studied the relationship between single-unit and population dynamics during different phases of an operant conditioning task. To examine the fine temporal relation between neural activity and behavior, we developed a model-based statistical analysis that captured behavioral idiosyncrasies. We found that single-unit responses to conditioned stimuli changed throughout the course of a session even under stable experimental conditions and consistent behavior. However, when behavioral responses to task contingencies had to be updated during the extinction phase, unitspecific modulations became coordinated across the whole population, pushing the network into a new stable attractor state. These results show that extinction learning is not associated with suppressed mPFC responses to conditioned stimuli, but is driven by single-unit coordination into population-wide transitions of the animal's internal state.

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“…Certainly, excitotoxic lesions of the IL have no effect on acquisition of appetitive Pavlovian-conditioned autoshaping (69) and NMDA antagonism of the IL has no effect on expression of instrumental conditioned responses at the start of extinction (70). Moreover, neither inactivation of the PL or IL affect the break point of a progressive ratio schedule (71). However, DHK-induced activation of IL, but not PL, increased the latency to approach, but had no effect on the consumption of, sucrose.…”

Section: Regulation Of Reward Processing In Areas 25/il and 32/pl Of mentioning

confidence: 98%

Why we need nonhuman primates to study the role of ventromedial prefrontal cortex in the regulation of threat- and reward-elicited responses

Roberts

Clarke

2019

Proc. Natl. Acad. Sci. U.S.A.

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The ventromedial prefrontal cortex (vmPFC) is consistently implicated in the cognitive and emotional symptoms of many psychiatric disorders, but the causal mechanisms of its involvement remain unknown. In part, this is because of the poor characterization of the disorders and their symptoms, and the focus of experimental studies in animals on subcortical (rather than cortical) dysregulation. Moreover, even in those experimental studies that have focused on the vmPFC, the preferred animal model for such research has been the rodent, in which there are marked differences in the organization of this region to that seen in humans, and thus the extent of functional homology is unclear. There is also a paucity of well-defined behavioral paradigms suitable for translating disorder-relevant findings across species. With these considerations in mind, we discuss the value of nonhuman primates (NHPs) in bridging the translational gap between human and rodent studies. We focus on recent investigations into the involvement in reward and threat processing of 2 major regions of the vmPFC, areas 25 and 32 in NHPs and their anatomical homologs, the infralimbic and prelimbic cortex, in rodents. We highlight potential similarities, but also differences between species, and consider them in light of the extent to which anatomical homology reflects functional homology, the expansion of the PFC in human and NHPs, and most importantly how they can guide future studies to improve the translatability of findings from preclinical animal studies into the clinic.

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Prelimbic and infralimbic cortical inactivations attenuate contextually driven discriminative responding for reward

Cited by 37 publications

References 66 publications

Divergent behavioral consequences of manipulations enhancing pyramidal neuron excitability in the prelimbic cortex

Divergent behavioral consequences of manipulations enhancing pyramidal neuron excitability in the prelimbic cortex

Coordinated prefrontal state transition leads extinction of reward-seeking behaviors

Why we need nonhuman primates to study the role of ventromedial prefrontal cortex in the regulation of threat- and reward-elicited responses

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