Neural correlates and determinants of approach–avoidance conflict in the prelimbic prefrontal cortex

Fernández-León, José A.; Engelke, Douglas Senna; Aquino-Miranda, Guillermo; Goodson, Alexandria; Rasheed, Maria N; Monte, Fabricio H Do

doi:10.7554/elife.74950

Cited by 26 publications

(20 citation statements)

References 120 publications

(162 reference statements)

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“…Adding to the known involvement of the RSC 55,56 and the Re 57–59 in modulating fear memory formation and expression, our results revealed neural activity in these structures was increased during mild memory recall, but not during strong memory recall, when compared to unshocked controls. Although the hippocampus 48,49,60–62 , prelimbic 63–65 , and cingulate cortex 66–68 are critical to contextual fear memory-related processes, we found no differences in their activation between groups, suggesting that the role of these structures in modulating the expression of fear of different intensities may not reflect in changes in overall activation levels.…”

Section: Discussioncontrasting

confidence: 75%

Network-Level Changes in the Brain Underlie Fear Memory Strength

Haubrich

Nader

2023

Preprint

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The strength of a fear memory significantly influences whether it drives adaptive or maladaptive behavior in the future. Yet, how mild and strong fear memories differ in underlying biology is not well understood. We hypothesized that this distinction may not be exclusively the result of changes within specific brain regions, but rather the outcome of collective changes in connectivity across multiple regions within the neural network. To test this, rats were fear conditioned in protocols of varying intensities to generate mild or strong memories. Neuronal activation driven by recall was measured using cfos immunohistochemistry in 12 brain regions implicated in fear learning and memory. The interregional coordinated brain activity was computed and graph-based functional networks were generated to compare how mild and strong fear memories differ at the systems level. Our results show that mild fear recall is supported by a well-connected brain network with small-world properties in which the amygdala is well-positioned to be modulated by other regions. In contrast, this connectivity is disrupted in strong fear memories and the amygdala is isolated from other regions. These findings indicate that the neural systems underlying mild and strong fear memories differ, with implications for understanding and treating disorders of fear dysregulation.

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Section: Discussioncontrasting

confidence: 75%

Network-Level Changes in the Brain Underlie Fear Memory Strength

Haubrich

Nader

2023

Preprint

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“…So, PVT could contribute to these changes in reward salience ( Zhu et al, 2018 ; Campus et al, 2019 ), response caution, or both. The PL is critical for approach–avoid decision-making ( Verharen et al, 2019 ; Kyriazi et al, 2020 ; Fernandez-Leon et al, 2022 ) and a major source of excitatory glutamatergic inputs driving PVT neuronal activity ( Vertes, 2002 ; Li and Kirouac, 2012 ; Otis et al, 2019 ). We hypothesized that the role of PVT likely depended on this prefrontal input.…”

Section: Resultsmentioning

confidence: 99%

“…The prelimbic cortex (PL) is well established in approach–avoid decision-making ( Verharen et al, 2019 ; Kyriazi et al, 2020 ; Fernandez-Leon et al, 2022 ). For example, activity of PL units during conflict reflects a variety of task variables (valence, trial identity, response) ( Kyriazi et al, 2020 ) that contribute to individual approach–avoid decisions ( Fernandez-Leon et al, 2022 ) and specifically control approach behaviors under threat ( Verharen et al, 2019 , 2020 ). These roles are due, at least in part, to prefrontal interactions with amygdala and striatum ( Verharen et al, 2019 , 2020 ; Kyriazi et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

A Corticothalamic Circuit Trades off Speed for Safety during Decision-Making under Motivational Conflict

et al. 2022

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Decisions to act while pursuing goals in the presence of danger must be made quickly but safely. Premature decisions risk injury or death whereas postponing decisions risk goal loss.Here we show how mice resolve these competing demands. Using microstructural behavioral analyses, we identified the spatiotemporal dynamics of approach-avoidance decisions under motivational conflict in male mice. Then we used cognitive modelling to show that these dynamics reflect the speeded decision-making mechanisms used by humans and non-human primates, with mice trading off decision speed for safety of choice when danger loomed. Using calcium imaging in paraventricular thalamus and optogenetic inhibition of the prelimbic cortex to paraventricular thalamus pathway, we show that this speed-safety trade off occurs because increases in paraventricular thalamus activity increase decision caution, thereby increasing approach-avoid decision times in the presence of danger. Our findings demonstrate that a discrete brain circuit involving the paraventricular thalamus and its prefrontal input adjusts decision caution during motivational conflict, trading off decision speed for decision safety when danger is close. We identify the corticothalamic pathway as central to cognitive control during decision-making under conflict.

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“…Additionally, in males, there was a positive correlation between alcohol seeking and neural activation in the mOFC, PrL, dBNST, NAcC, NAcSh, PVT, LHb, vSUB, and DG. These are all key regions implicated in learning, decision-making, reward seeking, punishment, and approach-avoidance behavior (Bannerman et al, 2004; Ch’ng et al, 2018; Fernandez-Leon et al, 2021; Haight & Flagel, 2014; Hsu et al, 2014; Kaouane et al, 2021; Marchant et al, 2016; McDannald et al, 2014; Rhodes & Murray, 2013; Rivera et al, 2019). Contrastingly, there were no correlations found in the females.…”

Section: Sex Differences In Reinstatement Of Alcohol Seekingmentioning

confidence: 99%

“…Additionally, in males, there was a positive correlation between alcohol seeking and neural activation in the mOFC, PrL, dBNST, NAcC, NAcSh, PVT, LHb, vSUB, and DG. These are all key regions implicated in learning, decisionmaking, reward seeking, punishment, and approach-avoidance behavior (Bannerman et al, 2004;Ch'ng et al, 2018;Fernandez-Leon This document is copyrighted by the American Psychological Association or one of its allied publishers.…”

Section: Brain Regions and Functional Connections Associated With Red...mentioning

confidence: 99%

Electric barrier-induced voluntary abstinence reduces alcohol seeking in male, but not female, iP rats.

Maddern,

Lawrence,

Campbell

2024

Behavioral Neuroscience

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Maintaining abstinence and preventing relapse are key to the successful recovery from alcohol use disorder. There are two main ways individuals with alcohol use disorder abstain from alcohol use: forced (e.g., incarceration) and voluntary. Voluntary abstinence is often evoked due to the negative consequences associated with excessive alcohol consumption. This study investigated relapse-like behavior to alcohol seeking following acute, forced, and voluntary abstinence. Male rats had increased operant self-administration responding throughout training compared to females; however, females consumed greater amounts of alcohol in g/kg. Both male and female rats achieved voluntary abstinence, which was induced using an electric barrier on the operant chamber floor with alcohol readily available during this period. Interestingly, male rats that underwent voluntary abstinence displayed reduced alcohol seeking compared to males in the acute and forced abstinence groups. This difference in alcohol seeking behavior across abstinence groups was not observed in female rats. Quantification of neuronal activation (Fos protein) revealed numerous brain regions (e.g., ventral subiculum and lateral habenula) to be associated with the reduced reinstatement propensity seen in male rats that underwent voluntary abstinence. Additionally, hierarchical clustering found enhanced functional connectivity and coordination in the male voluntary abstinence group compared to the male forced abstinence group. Collectively, these data implicate a sexual dimorphism in the effect that voluntary abstinence, at least in the model employed here, has on relapse-like behavior. This maybe driven by reduced neuronal activation at a network level and enhanced functional connectivity and integration.

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Neural correlates and determinants of approach–avoidance conflict in the prelimbic prefrontal cortex

Cited by 26 publications

References 120 publications

Network-Level Changes in the Brain Underlie Fear Memory Strength

Network-Level Changes in the Brain Underlie Fear Memory Strength

A Corticothalamic Circuit Trades off Speed for Safety during Decision-Making under Motivational Conflict

Electric barrier-induced voluntary abstinence reduces alcohol seeking in male, but not female, iP rats.

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