The Impacts of Early-life Adversity on Striatal and Hippocampal Memory Functions

Xu, Benke; Zhang, Xing; He, Yun; Liu, Cuiliu; Li, Lingrui; Li, Qun; Huang, Yan; Chen, Michael; Ren, Boxu; Guo, Yurong; Chen, Yuncai

doi:10.1016/j.neuroscience.2022.02.029

Cited by 11 publications

(39 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, the present study adds to emerging evidence that these commonly observed effects of adult stress on DLS habit memory may be mimicked by ELS. Consistent with the present findings, limited bedding, and nesting during postnatal days 2-9 results in greater habitual lever pressing in an instrumental learning task (Xu et al, 2022). Moreover, social isolation during adolescence in mice also enhanced habitual responding to the instrumental task during adulthood (Shan et al, 2022).…”

Section: Discussionsupporting

confidence: 89%

“…Notably, a recent study suggested that ELS-induced enhancement of DLS and impairment of the hippocampus may both be associated with habit memory enhancement in adulthood (Xu et al, 2022). In this study, ELS increased post-synaptic density and the number of thin and mushroom-shaped spines in the DLS, whereas opposite effects were found in the CA1 region of the hippocampal neurons (Xu et al, 2022).…”

Section: Discussionsupporting

confidence: 39%

“…This explanation would be consistent with recent evidence showing that behavioral stressors during childhood/adolescence may enhance habit memory during adulthood via altering structure and function of the dorsal striatum. Limited bedding and nesting during childhood in mice boosts habitual responding later in life, and this enhancement was associated with the increased post-synaptic density of neurons in the DLS (Xu et al, 2022). Moreover, ELS may be associated with suppression of the striatonigral direct pathway of the dorsomedial striatum (DMS; Shan et al, 2022), a brain region implicated in goal-directed actionoutcome learning as opposed to DLS-mediated habitual stimulus-response learning (Yin and Knowlton, 2006;Dezfouli and Balleine, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Although several studies have focused on the effects of ELS on hippocampal-dependent memory, there is some evidence that the enhanced use of DLS-dependent memory observed when emotional arousal is induced in adulthood may also be seen following ELS. In a recent study, limited bedding and nesting during post-natal days 2-9 resulted in greater habitual lever pressing in an instrumental learning task (Xu et al, 2022). Similarly, in human subjects, ELS is associated with greater adult use of habit memory strategies in solving instrumental learning tasks (Patterson et al, 2013(Patterson et al, , 2019Gordon et al, 2020), and prenatal stress has been similarly associated with increased used of striatal learning strategies in a virtual maze (Schwabe et al, 2012a).…”

Section: Introductionmentioning

confidence: 92%

See 3 more Smart Citations

Chronic corticosterone administration in adolescence enhances dorsolateral striatum-dependent learning in adulthood

Gadberry

Goodman²,

Packard³

2022

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Previous evidence indicates a link between early life stress (ELS) in humans and a predisposition to psychopathologies that are characterized in part by maladaptive habitual behaviors. Stress and anxiety influence the relative use of mammalian memory systems implicated in these disorders. Specifically, cognitive memory functions of the hippocampus are typically impaired by stress/anxiety, whereas habit memory functions of the dorsolateral striatum (DLS) are enhanced. A stress/anxiety bias toward habit memory has largely been demonstrated in adult rodents and humans, and the effects of ELS on the later use of DLS-dependent habit memory in adult rodents have not been extensively examined. The present study addressed this question by chronically elevating corticosterone (CORT) during adolescence, and investigated the effects of this treatment on DLS-dependent habit learning in adulthood. In experiment 1, adolescent rats received a single daily injection of either CORT (5 mg/kg) or vehicle (cVEH) over 5 days and then matured undisturbed before training as adults in a DLS-dependent water plus-maze task. Rats administered CORT injections during adolescence displayed a strong trend toward enhanced learning during adulthood relative to vehicle-treated rats. Adolescent CORT administration also increased anxiety-like behavior in adulthood in an elevated plus-maze. In experiment 2, adolescent CORT administration enhanced task acquisition in adulthood, and this effect was blocked by concurrent administration of the glucocorticoid antagonist mifepristone (30 mg/kg). Taken together, these findings suggest that chronic elevation of glucocorticoids during adolescence are sufficient to facilitate habit learning in adulthood, and indicate that glucocorticoid function may be a potential underlying mechanism by which ELS influences subsequent habitual behaviors.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 39%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

See 2 more Smart Citations

Chronic corticosterone administration in adolescence enhances dorsolateral striatum-dependent learning in adulthood

Gadberry

Goodman²,

Packard³

2022

Front. Behav. Neurosci.

View full text Add to dashboard Cite

show abstract

“…These synaptic signatures could drive the lasting microglial (mal-) adaptations, as we found in our adult data, where the early-life condition of both synaptosomes and microglia contributed to reduced synaptic uptake, possibly ultimately contributing to the well-established ELS effects on hippocampal plasticity (40,89,90). The downregulation of synaptic phagocytosis by P200 ELS microglia might seem counterintuitive considering the literature on ELS-induced reduction of dendritic and synaptic complexity (91)(92)(93), which would imply increased phagocytosis. In fact, we observed upregulation of genes regulating phagocytosis (e.g.…”

Section: Els Impacts On Microglial Phagocytosis Of Synaptosomesmentioning

confidence: 55%

Early-life stress lastingly impacts microglial transcriptome and function under basal and immune-challenged conditions

Reemst¹,

Kracht

Kotah

et al. 2022

Preprint

View full text Add to dashboard Cite

Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depression later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but how ELS impacts microglia, the main tissue-resident macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS induced by limited bedding and nesting material during the first week of life (postnatal days [P]2–9) on microglial i) morphology; ii) hippocampal gene expression; and iii) synaptosome phagocytic capacity in male pups (P9) and adult (P200) mice. The hippocampus of ELS-exposed adult mice displayed altered proportions of morphological subtypes of microglia, as well as microglial transcriptomic changes related to the tumor necrosis factor response and protein ubiquitination. ELS exposure leads to distinct gene expression profiles during microglial development from P9 to P200 and in response to an LPS challenge at P200. Functionally, synaptosomes from ELS-exposed mice were phagocytosed less by age-matched microglia. At P200, but not P9, ELS microglia showed reduced synaptosome phagocytic capacity when compared to CTRL microglia. Lastly, we confirmed the ELS-induced increased expression of the phagocytosis-related gene GAS6 that we observed in mice, in the dentate gyrus of individuals with a history of child abuse using in situ hybridization. These findings reveal persistent effects of ELS on microglial function and suggest that altered microglial phagocytic capacity is a key contributor to ELS-induced phenotypes.

show abstract

Introduction to the Special Issue on the Exposome—Understanding Environmental Impacts on Brain Development and Risk for Psychopathology

Barch

2022

Biological Psychiatry Global Open Science

View full text Add to dashboard Cite

The Impacts of Early-life Adversity on Striatal and Hippocampal Memory Functions

Cited by 11 publications

References 69 publications

Chronic corticosterone administration in adolescence enhances dorsolateral striatum-dependent learning in adulthood

Chronic corticosterone administration in adolescence enhances dorsolateral striatum-dependent learning in adulthood

Early-life stress lastingly impacts microglial transcriptome and function under basal and immune-challenged conditions

Introduction to the Special Issue on the Exposome—Understanding Environmental Impacts on Brain Development and Risk for Psychopathology

Contact Info

Product

Resources

About