Maturation of amygdala inputs regulate shifts in social and fear behaviors: A substrate for developmental effects of stress

Ferrara, Nicole C.; Trask, Sydney; Rosenkranz, J. Amiel

doi:10.1016/j.neubiorev.2021.01.021

Cited by 25 publications

(15 citation statements)

References 238 publications

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“…We further evaluated whether the social functioning changes induced by the menthol flavor in ENDS are associated with any alternations on innate visual or perceptual behaviors ( Ferrara et al, 2021 ; Sakurai, 2021 ; Wei et al, 2021 ). Behavioral paradigms, such as innate fear and heat pain response were used in our experiments.…”

Section: Resultsmentioning

confidence: 99%

Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings

Tian

et al. 2022

Front. Mol. Neurosci.

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The use of electronic cigarette (e-cigarette) has been increasing dramatically worldwide. More than 8,000 flavors of e-cigarettes are currently marketed and menthol is one of the most popular flavor additives in the electronic nicotine delivery systems (ENDS). There is a controversy over the roles of e-cigarettes in social behavior, and little is known about the potential impacts of flavorings in the ENDS. In our study, we aimed to investigate the effects of menthol flavor in ENDS on the social behavior of long-term vapor-exposed mice with a daily intake limit, and the underlying immunometabolic changes in the central and peripheral systems. We found that the addition of menthol flavor in nicotine vapor enhanced the social activity compared with the nicotine alone. The dramatically reduced activation of cellular energy measured by adenosine 5′ monophosphate-activated protein kinase (AMPK) signaling in the hippocampus were observed after the chronic exposure of menthol-flavored ENDS. Multiple sera cytokines including C5, TIMP-1, and CXCL13 were decreased accordingly as per their peripheral immunometabolic responses to menthol flavor in the nicotine vapor. The serum level of C5 was positively correlated with the alteration activity of the AMPK-ERK signaling in the hippocampus. Our current findings provide evidence for the enhancement of menthol flavor in ENDS on social functioning, which is correlated with the central and peripheral immunometabolic disruptions; this raises the vigilance of the cautious addition of various flavorings in e-cigarettes and the urgency of further investigations on the complex interplay and health effects of flavoring additives with nicotine in e-cigarettes.

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Section: Resultsmentioning

confidence: 99%

Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings

Tian

et al. 2022

Front. Mol. Neurosci.

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“…In Tbr1 +/− mice, dietary zinc supplementation prevents impairments in auditory fear memory and social interaction, but not social novelty recognition impairments. This selective therapeutic effect of dietary zinc supplementation may be attributed to (1) differences in brain circuitry and regions involved in distinct social behaviours [ 83 , 84 ], (2) discrete zinc responsiveness in different neural pathways [ 72 , 85 ], and (3) timing of zinc supplementation [ 86 ]. The detrimental behavioural phenotypes induced by Tbr1 haploinsufficiency likely manifest from early stages in brain development [ 17 , 20 , 24 – 26 ].…”

Section: Discussionmentioning

confidence: 99%

Dietary zinc supplementation rescues fear-based learning and synaptic function in the Tbr1+/− mouse model of autism spectrum disorders

et al. 2022

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Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by a dyad of behavioural symptoms—social and communication deficits and repetitive behaviours. Multiple aetiological genetic and environmental factors have been identified as causing or increasing the likelihood of ASD, including serum zinc deficiency. Our previous studies revealed that dietary zinc supplementation can normalise impaired social behaviours, excessive grooming, and heightened anxiety in a Shank3 mouse model of ASD, as well as the amelioration of synapse dysfunction. Here, we have examined the efficacy and breadth of dietary zinc supplementation as an effective therapeutic strategy utilising a non-Shank-related mouse model of ASD—mice with Tbr1 haploinsufficiency. Methods We performed behavioural assays, amygdalar slice whole-cell patch-clamp electrophysiology, and immunohistochemistry to characterise the synaptic mechanisms underlying the ASD-associated behavioural deficits observed in Tbr1+/− mice and the therapeutic potential of dietary zinc supplementation. Two-way analysis of variance (ANOVA) with Šídák's post hoc test and one-way ANOVA with Tukey’s post hoc multiple comparisons were performed for statistical analysis. Results Our data show that dietary zinc supplementation prevents impairments in auditory fear memory and social interaction, but not social novelty, in the Tbr1+/− mice. Tbr1 haploinsufficiency did not induce excessive grooming nor elevate anxiety in mice. At the synaptic level, dietary zinc supplementation reversed α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartate receptor (NMDAR) hypofunction and normalised presynaptic function at thalamic-lateral amygdala (LA) synapses that are crucial for auditory fear memory. In addition, the zinc supplemented diet significantly restored the synaptic puncta density of the GluN1 subunit essential for functional NMDARs as well as SHANK3 expression in both the basal and lateral amygdala (BLA) of Tbr1+/− mice. Limitations The therapeutic effect of dietary zinc supplementation observed in rodent models may not reproduce the same effects in human patients. The effect of dietary zinc supplementation on synaptic function in other brain structures affected by Tbr1 haploinsufficiency including olfactory bulb and anterior commissure will also need to be examined. Conclusions Our data further the understanding of the molecular mechanisms underlying the effect of dietary zinc supplementation and verify the efficacy and breadth of its application as a potential treatment strategy for ASD.

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“…It is well described that local amygdala networks mediate the acquisition, expression and extinction of conditioned fear, and regulate social behaviors (Duvarci & Pare, 2014;Ferrara et al, 2021). Also, that experience-dependent increases in synaptic strength of excitatory projections from the lateral nucleus of the amygdala into the BLA (LA to BLA) controls encoding of anxiety-like behaviors and other emotion-related behavioral responses (Nonaka et al, 2014;Bocchio et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Late-Onset Behavioral and Synaptic Consequences of L-Type Ca²⁺Channel Activation in the Basolateral Amygdala of Developing Rats

Zhang

Sack

Jones

et al. 2022

eNeuro

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Maturation of amygdala inputs regulate shifts in social and fear behaviors: A substrate for developmental effects of stress

Cited by 25 publications

References 238 publications

Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings

Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings

Dietary zinc supplementation rescues fear-based learning and synaptic function in the Tbr1+/− mouse model of autism spectrum disorders

Late-Onset Behavioral and Synaptic Consequences of L-Type Ca²⁺Channel Activation in the Basolateral Amygdala of Developing Rats

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Maturation of amygdala inputs regulate shifts in social and fear behaviors: A substrate for developmental effects of stress

Cited by 25 publications

References 238 publications

Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings

Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings

Dietary zinc supplementation rescues fear-based learning and synaptic function in the Tbr1+/− mouse model of autism spectrum disorders

Late-Onset Behavioral and Synaptic Consequences of L-Type Ca2+Channel Activation in the Basolateral Amygdala of Developing Rats

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Late-Onset Behavioral and Synaptic Consequences of L-Type Ca²⁺Channel Activation in the Basolateral Amygdala of Developing Rats