Adolescent social isolation induces distinct changes in the medial and lateral OFC-BLA synapse and social and emotional alterations in adult mice

Kuniishi, Hiroshi; Nakatake, Yuko; Sekiguchi, Masayuki; Yamada, Mitsuhiko

doi:10.1038/s41386-022-01358-6

“…Notably, dorsal raphe dopamine neurons have increased AMPA/NMDA ratio when moved from group housed to isolated housing, yet social-isolation induced plasticity does not occur in VTA dopamine neurons (Matthews et al, 2016). In the OFC, 5 weeks adolescent social isolation from weaning increases the AMPA/NMDA ratio through postsynaptic mechanisms at lOFC-BLA synapses and decreases parvalbumin expression in the OFC of adolescent female, but not male mice (Kuniishi et al, 2022; Jeon et al, 2023). It is not known if these changes in OFC function occur with 7-day isolation during adulthood.…”

Section: Discussionmentioning

confidence: 98%

Short- and long-term high-fat diet exposure differentially alters phasic and tonic GABAergic signaling onto lateral orbitofrontal pyramidal neurons

Seabrook

¹

,

Peterson

²

,

Noble

³

et al. 2023

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0

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The chronic consumption of caloric dense high-fat foods is a major contributor to increased body weight, obesity, and other chronic health conditions. The orbitofrontal cortex (OFC) is critical in guiding decisions about food intake and is altered with diet-induced obesity. Obese rodents have altered morphological and synaptic electrophysiological properties in the lateral OFC. Yet the time course by which exposure to a high-fat diet (HFD) induces these changes is poorly understood. Here mice are exposed to either short- (7 day) or long-term (90 day) HFD. Long-term HFD exposure increases body weight, and glucose signaling compared to short-term HFD or a standard chow control diet (SCD). Both short and long-term HFD exposure increased the excitability of lOFC pyramidal neurons. However, phasic and tonic GABAergic signalling was differentially altered depending on HFD exposure length, such that tonic GABAergic signaling was decreased with early exposure to the HFD and phasic signaling was changed with long-term diet exposure. Furthermore, alterations in the short-term diet exposure were transient, as removal of the diet restored electrophysiological characteristics similar to mice fed SCD whereas long-term HFD electrophysiological changes were persistent and remained after HFD removal. Finally, we demonstrate that changes in reward devaluation occur early with diet exposure. Together, these results suggest that the duration of HFD exposure differentially alters lOFC function and provides mechanistic insights into the susceptibility of the OFC to impairments in outcome devaluation.

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“…Notably, dorsal raphe dopamine neurons have increased AMPA/NMDA ratio when moved from group housed to isolated housing, yet social-isolation induced plasticity does not occur in VTA dopamine neurons ( Matthews et al, 2016 ). In the OFC, five weeks adolescent social isolation from weaning increases the AMPA/NMDA ratio through postsynaptic mechanisms at lOFC-BLA synapses and decreases parvalbumin expression in the OFC of adolescent female, but not male mice ( Kuniishi et al, 2022 ; Jeon et al, 2023 ). It is not known whether these changes in OFC function occur with 7-d isolation during adulthood.…”

Section: Discussionmentioning

confidence: 99%

Short- and Long-Term High-Fat Diet Exposure Differentially Alters Phasic and Tonic GABAergic Signaling onto Lateral Orbitofrontal Pyramidal Neurons

Seabrook,

Peterson,

Noble

et al. 2023

J. Neurosci.

1

0

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The chronic consumption of caloric dense high-fat foods is a major contributor to increased body weight, obesity, and other chronic health conditions. The orbitofrontal cortex (OFC) is critical in guiding decisions about food intake and is altered with diet-induced obesity. Obese rodents have altered morphological and synaptic electrophysiological properties in the lateral orbitofrontal cortex (lOFC). Yet the time course by which exposure to a high-fat diet (HFD) induces these changes is poorly understood. Here male mice are exposed to either short- (7 day) or long-term (90 day) HFD. Long-term HFD exposure increases body weight, and glucose signaling compared to short-term HFD or a standard chow control diet (SCD). Both short and long-term HFD exposure increased the excitability of lOFC pyramidal neurons. However, phasic and tonic GABAergic signalling was differentially altered depending on HFD exposure length, such that tonic GABAergic signaling was decreased with early exposure to the HFD and phasic signaling was changed with long-term diet exposure. Furthermore, alterations in the short-term diet exposure were transient, as removal of the diet restored electrophysiological characteristics similar to mice fed SCD whereas long-term HFD electrophysiological changes were persistent and remained after HFD removal. Finally, we demonstrate that changes in reward devaluation occur early with diet exposure. Together, these results suggest that the duration of HFD exposure differentially alters lOFC function and provides mechanistic insights into the susceptibility of the OFC to impairments in outcome devaluation.Significant StatementThis study provides mechanistic insight on the impact of short- and long-term high fat diet (HFD) exposure on GABAergic function in the lateral orbitofrontal cortex (lOFC), a region known to guide decision making. We find short-term HFD exposure induces transient changes in firing and tonic GABA action on lOFC pyramidal neurons, whereas long-term HFD induces obesity and has lasting changes on firing, tonic GABA and inhibitory synaptic transmission onto lOFC neurons. Given that GABAergic signaling in the lOFC can influence decision making around food, these results have important implications in present society as palatable energy dense foods are abundantly available.

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“…Repeated footshock stress at PND21 led to an increase in social interaction in males in adulthood [20]. Although there is some congruence in the literature, not all studies examining the impact of post-weaning social isolation on social preference find consistent results [21]. These discrepancies may be impacted by the age at testing.…”

Section: Post-weaning Social Isolation Stress Leads To Sex-specific E...mentioning

confidence: 98%

Post-weaning social isolation alters sociability in a sex-specific manner

Myers,

Birmingham,

Rhoads

et al. 2024

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Adolescence is a critical period for brain development in humans and stress exposure during this time can have lasting effects on behavior and brain development. Social isolation and loneliness are particularly salient stressors that lead to detrimental mental health outcomes particularly in females, although most of the preclinical work on social isolation has been done in male animals. Our lab has developed a model of post-weaning adolescent social isolation that leads to increased drug reward sensitivity and altered neuronal structure in limbic brain regions. The current study utilized this model to determine the impact of adolescent social isolation on a three-chamber social interaction task both during adolescence and adulthood. We found that while post-weaning isolation does not alter social interaction during adolescence (PND45), it has sex-specific effects on social interaction in adulthood (PND60), potentiating social interaction in male mice and decreasing it in female mice. As early life stress can activate microglia leading to alterations in neuronal pruning, we next examined the impact of inhibiting microglial activation with daily minocycline administration during the first three weeks of social isolation on these changes in social interaction. During adolescence, minocycline dampened social interaction in male mice, while having no effect in females. In contrast, during adulthood, minocycline did not alter the impact of adolescent social isolation in males, with socially isolated males exhibiting higher levels of social interaction compared to their group housed counterparts. In females, adolescent minocycline treatment reversed the effect of social isolation leading to increased social interaction in the social isolation group, mimicking what is seen in naïve males. Taken together, adolescent social isolation leads to sex-specific effects on social interaction in adulthood and adolescent minocycline treatment alters the effects of social isolation in females, but not males.

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Adolescent social isolation induces distinct changes in the medial and lateral OFC-BLA synapse and social and emotional alterations in adult mice

Cited by 17 publications

References 81 publications

Short- and long-term high-fat diet exposure differentially alters phasic and tonic GABAergic signaling onto lateral orbitofrontal pyramidal neurons

Short- and long-term high-fat diet exposure differentially alters phasic and tonic GABAergic signaling onto lateral orbitofrontal pyramidal neurons

Short- and Long-Term High-Fat Diet Exposure Differentially Alters Phasic and Tonic GABAergic Signaling onto Lateral Orbitofrontal Pyramidal Neurons

Post-weaning social isolation alters sociability in a sex-specific manner

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