Transient food insecurity during the juvenile-adolescent period affects adult weight, cognitive flexibility, and dopamine neurobiology

Lin, Wan Chen; Liu, Christine; Kosillo, Polina; Tai, Lung-Hao; Galarce, Ezequiel M.; Bateup, Helen S.; Lammel, Stephan; Wilbrecht, Linda

doi:10.1016/j.cub.2022.06.089

Cited by 21 publications

(8 citation statements)

References 76 publications

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“…Here, our evidence suggests that nicotine in adolescence “freezes” VTA-NAc and VTA-AMg DA circuits in their adolescent state. This stalling of developing DA circuits in response to experience is likely not limited to nicotine, or even drug exposure, as similar changes in glutamate plasticity onto VTA DA neurons have been reported after food insecurity in adolescence 99 . This raises important questions in the cross-sensitivity and additive relationship between stress and drug use in adolescence and adulthood.…”

Section: Discussionsupporting

confidence: 53%

Nicotine in adolescence freezes dopamine circuits in an immature state

Reynolds,

Gulmez,

Fayad

et al. 2023

Preprint

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Nicotine use during adolescence is largely associated with negative long-term outcomes, including addiction to nicotine in adulthood. How nicotine acts on developing neurocircuitry in adolescence remains largely unknown, but may hold the key for informing more effective intervention efforts. We found transient nicotine exposure in early adolescence was sufficient for adult mice to show a marked vulnerability to nicotine. Brain-wide activity mapping showed that these mice had an enhanced response to an acute nicotine injection and widespread disruption of functional connectivity in comparison to controls, particularly within dopaminergic networks. Neurophysiological analysis further revealed that their ventral tegmental area (VTA) dopamine neurons show an immature basal plasticity signature and an adolescent-like imbalance in nicotine-induced activity between nucleus accumbens (NAc) and amygdala (AMG)-projecting pathways, known to respectively produce the reinforcing and anxiogenic effects of nicotine. The anxiogenic effect of nicotine is abolished in adult mice treated with nicotine in adolescence, strongly resembling the normal phenotype of young mice. Together these results suggest that nicotine exposure in adolescence somehow “froze” both their neural circuit and behavioral reaction to nicotine, carrying an adolescent-like vulnerability to the drug into adulthood. Finally, we are able to “thaw” the behavioral response to acute nicotine in adolescent-exposed mice by chemogenetically resetting the balance between the underlying NAc- and AMG-projecting dopamine circuits, restoring a mature anxiety-like response to acute nicotine. Together, our results highlight how diverse dopamine pathways can be impacted by experience in adolescence, and further suggest that the perseverance of a developmental imbalance between dopamine pathways may alter vulnerability profiles for later dopamine-dependent psychopathologies.

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Section: Discussionsupporting

confidence: 53%

Nicotine in adolescence freezes dopamine circuits in an immature state

Reynolds,

Gulmez,

Fayad

et al. 2023

Preprint

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“…With growing interest in understanding the physiological impacts of FI, mammalian models are required, and animal models of FI in rats and mice are starting to appear [ 60 – 62 ]. In a recent experiment, female Sprague-Dawley rats were assigned for 12 weeks to either an insecure condition, in which there was unpredictable variation in the number and size of meals a day, or a control, in which, the number and size of daily meals was constant and energy intake was fixed to be identical to the mean intake in the insecure condition ([ 61 ] experiment 2).…”

Section: Does Food Insecurity Cause Weight Gain?mentioning

confidence: 99%

Food insecurity as a cause of adiposity: evolutionary and mechanistic hypotheses

Bateson,

Pepper

2023

Phil. Trans. R. Soc. B

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Food insecurity (FI) is associated with obesity among women in high-income countries. This seemingly paradoxical association can be explained by the insurance hypothesis, which states that humans possess evolved mechanisms that increase fat storage to buffer against energy shortfall when access to food is unpredictable. The evolutionary logic underlying the insurance hypothesis is well established and experiments on animals confirm that exposure to unpredictable food causes weight gain, but the mechanisms involved are less clear. Drawing on data from humans and other vertebrates, we review a suite of behavioural and physiological mechanisms that could increase fat storage under FI. FI causes short-term hyperphagia, but evidence that it is associated with increased total energy intake is lacking. Experiments on animals suggest that unpredictable food causes increases in retained metabolizable energy and reductions in energy expenditure sufficient to fuel weight gain in the absence of increased food intake. Reducing energy expenditure by diverting energy from somatic maintenance into fat stores should improve short-term survival under FI, but the trade-offs potentially include increased disease risk and accelerated ageing. We conclude that exposure to FI plausibly causes increased adiposity, poor health and shorter lifespan. This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part II)’.

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“…Indeed, in individuals with ASD, the severity of RRBs is associated with measures of cognitive inflexibility, and evidence from imaging studies suggests that altered corticostriatal connectivity may be present in the case of both repetitive behaviors and cognitive inflexibility (Uddin, 2021). To assess cognitive flexibility in Cntnap2 -/- mice, we utilized a four-choice odor-based reversal learning assay (Johnson et al, 2016; Lin et al, 2022). Briefly, mice are trained to dig for a reward in one of four pots containing scented wood shavings (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The DMS and ventral striatum (nucleus accumbens) have been shown to play an important role in reversal learning (Izquierdo et al, 2017), and in the four choice task specifically (Delevich et al, 2022). Additionally, decreased dopamine release in the DLS is associated with deficits in reversal learning in this task (Kosillo et al, 2019; Lin et al, 2022). Together, the learning phenotypes seen in Cntnap2 -/- mice in the accelerating rotarod and reversal learning assay share an underlying rigidity in behavioral choice.…”

Section: Discussionmentioning

confidence: 99%

Cntnap2loss drives striatal neuron hyperexcitability and behavioral inflexibility

Cording,

Tu,

Wang

et al. 2024

Preprint

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by two major diagnostic criteria - persistent deficits in social communication and interaction, and the presence of restricted, repetitive patterns of behavior (RRBs). Evidence from both human and animal model studies of ASD suggest that alteration of striatal circuits, which mediate motor learning, action selection, and habit formation, may contribute to the manifestation of RRBs. CNTNAP2 is a syndromic ASD risk gene, and loss of function of Cntnap2 in mice is associated with RRBs. How loss of Cntnap2 impacts striatal neuron function is largely unknown. In this study, we utilized Cntnap2-/- mice to test whether altered striatal neuron activity contributes to aberrant motor behaviors relevant to ASD. We find that Cntnap2-/- mice exhibit increased cortical drive of striatal projection neurons (SPNs), with the most pronounced effects in direct pathway SPNs. This enhanced drive is likely due to increased intrinsic excitability of SPNs, which make them more responsive to cortical inputs. We also find that Cntnap2-/- mice exhibit spontaneous repetitive behaviors, increased motor routine learning, and cognitive inflexibility. Increased corticostriatal drive, in particular of the direct pathway, may contribute to the acquisition of repetitive, inflexible behaviors in Cntnap2 mice.

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Transient food insecurity during the juvenile-adolescent period affects adult weight, cognitive flexibility, and dopamine neurobiology

Cited by 21 publications

References 76 publications

Nicotine in adolescence freezes dopamine circuits in an immature state

Nicotine in adolescence freezes dopamine circuits in an immature state

Food insecurity as a cause of adiposity: evolutionary and mechanistic hypotheses

Cntnap2loss drives striatal neuron hyperexcitability and behavioral inflexibility

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