Exposure to unpredictable maternal sensory signals influences cognitive development across species

Davis, Elizabeth L.; Stout, Stephanie A.; Molet, Jenny; Vegetabile, Brian G.; Glynn, Laura M.; Sandman, Curt A.; Heins, Kevin; Stern, Hal S.; Baram, Tallie Z.

doi:10.1073/pnas.1703444114

Cited by 143 publications

(261 citation statements)

References 38 publications

(49 reference statements)

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“…The pattern of F0 maternal care resulting from exposure to the LN condition was largely in line with earlier findings using this model (Davis et al, 2017; Knop et al, 2019; Molet et al, 2016; Rice et al, 2008). While different pup-directed maternal behaviors remained relatively unaltered, the unpredictability of maternal behavior, particularly on the nest site, increased.…”

Section: Discussionsupporting

confidence: 88%

“…We selected two rodent models developed to chronically induce alterations in the quality and quantity of parental care received by offspring. First, limited availability of nesting and bedding (LN) material to a mouse dam was used to induce an adverse early life environment; this model increases unpredictability of maternal care received by the pups (Davis et al, 2017; Knop et al, 2019; Molet et al, 2016), leading to increased corticosterone levels in pups (Rice et al, 2008) and altered offspring development and behavior in adulthood (Bonapersona et al, 2019; Walker et al, 2017). Second, as beneficial and stimulating social rearing environment we selected a communal nesting (CN) condition, where two or more dams share care-giving behavior towards multiple litters (Branchi et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Maternal care of heterozygous Dopamine Receptor D4 knockout mice: Differential susceptibility to early-life rearing conditions

Knop

IJzendoorn

Bakermans‐Kranenburg

et al. 2019

Preprint

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AbstractThe differential susceptibility hypothesis proposes that individuals who are more susceptible to the negative effects of adverse rearing conditions may also benefit more from enriched environments. Evidence derived from human experiments suggests the lower efficacy dopamine receptor D4 (DRD4) 7-repeat as a main factor in exhibiting these for better and for worse characteristics. However, human studies lack the genetic and environmental control offered by animal experiments, complicating assessment of causal relations. To study differential susceptibility in an animal model, we exposed Drd4+/- mice and control litter mates to a limited nesting/bedding (LN), standard nesting (SN) or communal nesting (CN) rearing environment from postnatal day (P) 2-14. Puberty onset was examined from P24-P36 and adult females were assessed on maternal care towards their own offspring. In both males and females, LN reared mice showed a delay in puberty onset that was partly mediated by a reduction in body weight at weaning, irrespective of Drd4 genotype. During adulthood, LN reared females exhibited characteristics of poor maternal care, whereas dams reared in CN environments showed lower rates of unpredictability towards their own offspring. Differential susceptibility was observed only for licking/grooming levels of female offspring towards their litter; LN reared Drd4+/- mice exhibited the lowest and CN reared Drd4+/- mice the highest levels of licking/grooming. These results indicate that both genetic and early-environmental factors play an important role in shaping maternal care of the offspring for better and for worse.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Maternal care of heterozygous Dopamine Receptor D4 knockout mice: Differential susceptibility to early-life rearing conditions

Knop

IJzendoorn

Bakermans‐Kranenburg

et al. 2019

Preprint

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“…The specific aspects of early-life adversity that cause these effects and the mechanisms by which ELA generates addiction-like behavior remain to be explored. Our prior work demonstrated that ELA (using our naturalistic LBN model) is characterized by chaotic, unpredictable maternal signals to the developing pups 20 , and converging evidence from both humans and rodents shows that such unpredictable, fragmented early-life environments profoundly impact brain function later in life 21 . We propose that these long-term negative outcomes, including opioid addiction risk, result from aberrant maturation of specific brain circuits, a finding emerging with the use of translatable methods such as structural magnetic resonance imaging 8 .…”

mentioning

confidence: 84%

On the early-life origins of vulnerability to opioid addiction

Levis

Bentzley

Molet

et al. 2019

Preprint

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The origins and neural bases of the current opioid addiction epidemic are unclear. Genetics plays a major role in addiction vulnerability, but cannot account for the recent exponential rise in opioid abuse, so environmental factors must contribute. Individuals with history of early-life adversity (ELA) are disproportionately prone to opioid addiction, yet whether ELA directly influences brain development and function to cause this vulnerability is unknown. We simulated ELA in female rats, which provoked a profound opioid-addiction vulnerability. This was characterized by resistance to extinction, increased relapse-like behavior, and, as in addicted humans, major increases in opioid economic demand. By contrast, seeking of less salient natural rewards was unaffected by ELA, whereas demand for highly palatable treats was augmented. These discoveries provide novel insights into the origins and nature of reward circuit malfunction that may set the stage for addiction. The Limited Bedding and Nesting (LBN) model of early-life adversityOn PD2, pups from at least two litters were gathered, and pups were assigned at random to each dam in equal numbers of male and female to prevent potential confounding effect of genetic variables or litter size. Dams and pups assigned to the LBN group were transferred to cages fitted with a plastic-coated mesh platform sitting ∼ 2.5 cm above the cage floor. Bedding sparsely covered the cage floor under the platform, and one-half of a 24.2 cm × 23.5 cm paper towel was provided for nesting material. Control group (CTL) dams and pups were placed in cages containing a standard amount of bedding (∼0.33 cubic feet of shredded corn cob) without a platform, and one full paper towel. CTL and LBN cages remained undisturbed during PD2-9, during which maternal behaviors were monitored as previously described 12-14 . On PD10, animals were all transferred to CTL condition cages. Intravenous catheter surgeryAt approximately PD70, rats were deeply anesthetized with isoflurane (2-2.5%) and chronic indwelling catheters were inserted into the right jugular vein, exiting two cm caudal to the scapulae. Meloxicam (1mg/kg, i.p.) for postsurgical analgesia, and prophylactic antibiotic cefazolin (0.2ml, i.v.; 10mg/0.1ml) were given perioperatively. After 5 days of recovery, catheters were flushed daily following each opioid self-administration session with cefazolin (10mg/0.1ml) and heparin lock solution (10 U/0.1ml) to maintain catheter patency.

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“…Syllable labels, onset times, and offset times were exported to R for further analysis. Entropy rate was calculated using the ccber package in R (Davis et al, 2017) for each bird based on the syllable labels, including a label reflecting the start or end of a song file. Entropy rate reflects an overall measure of the predictability of syllable transitions as a first order Markov chain, calculated according to the formula: …”

Section: Methodsmentioning

confidence: 99%

Autism-linked gene FoxP1 selectively regulates the cultural transmission of learned vocalizations

García-Oscos

Koch

Pancholi

et al. 2020

Preprint

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Autism spectrum disorders (ASD) are characterized by impaired learning of culturally transmitted behaviors like 10 social skills, speech, and language 1-3 . These behaviors are learned by copying parents and other social models during 11 development, a two-stage process that involves forming memories of appropriate behaviors during social 12 experiences and then using those memories to guide imitation. How ASD-linked genes impair these often-13 intertwined aspects of learning is not known, thereby limiting our understanding of the developmental progression 14 of ASD and the targeting of therapeutic interventions. Here we show that these aspects of learning are dissociable 15 and that the ASD-linked gene FoxP1 selectively impairs learning from social experience, but not behavioral imitation. 16 Haploinsufficiency of FOXP1 in humans causes FOXP1 syndrome, a neurodevelopmental disorder typified by severe 17 disruptions in speech and language development, and other ASD-associated symptoms 4,5 . We tested how 18 knockdown of FoxP1 (FP1-KD) affects the cultural transmission of vocal behaviors in zebra finches, a songbird that 19 learns by memorizing and vocally copying the song of an adult 'song-tutor'. We find that FP1-KD blocks song learning20 in juvenile birds by selectively impairing their ability to encode a memory during social experiences with a song-21 tutor. These learning deficits are linked to disruptions in experience-driven structural and functional plasticity. 22However, if birds are exposed to tutor-song prior to FP1-KD, their ability to imitate that song during development is 23 unaffected. Thus, FP1-KD impairs cultural transmission of vocalizations by disrupting the ability to form appropriate 24 vocal memories, yet spares the ability to use previously acquired memories to guide vocal learning. This indicates 25 that learning from social experience may be particularly vulnerable in FOXP1 syndrome. 26 27 28Humans and other animals learn many of their complex and socially oriented behaviors by imitating more experienced 29 individuals in their environment. For example, development of spoken language is rooted in a child's ability to imitate 30 the speech patterns of their parent(s) and other adults 6-8 . This cultural transmission of behavior is impaired in many 31 neurodevelopmental disorders, most notably ASD 1-3 . However, how ASD risk genes impact behavioral imitation is still 32 not known. We sought to examine this issue by testing the role of FoxP1 in the cultural transmission of song between 33 adult and juvenile zebra finches ( Fig. 1a-d, Extended Data Fig. 1). 34 35 2 FOXP1 (forkhead-box protein 1) is one of the top ASD-associated genes, and its haploinsufficiency causes specific 36 language impairment and intellectual disability in children 5 . FoxP1 is expressed in many of the same areas of the pallium 37 and basal ganglia in mammals and songbirds 9-11 . In zebra finches, FoxP1 expression is enriched in many brain regions 38 that are known to be important for song learning [10][11][12] (Fig. ...

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Exposure to unpredictable maternal sensory signals influences cognitive development across species

Cited by 143 publications

References 38 publications

Maternal care of heterozygous Dopamine Receptor D4 knockout mice: Differential susceptibility to early-life rearing conditions

Maternal care of heterozygous Dopamine Receptor D4 knockout mice: Differential susceptibility to early-life rearing conditions

On the early-life origins of vulnerability to opioid addiction

Autism-linked gene FoxP1 selectively regulates the cultural transmission of learned vocalizations

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