| 1. |
- Opendak, Maya, et al.
(författare)
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Neurobiology of maternal regulation of infant fear : the role of mesolimbic dopamine and its disruption by maltreatment
- 2019
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Ingår i: Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X .- 1740-634X. ; 44:7, s. 1247-1257
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Tidskriftsartikel (refereegranskat)abstract
- Child development research highlights caregiver regulation of infant physiology and behavior as a key feature of early life attachment, although mechanisms for maternal control of infant neural circuits remain elusive. Here we explored the neurobiology of maternal regulation of infant fear using neural network and molecular levels of analysis in a rodent model. Previous research has shown maternal suppression of amygdala-dependent fear learning during a sensitive period. Here we characterize changes in neural networks engaged during maternal regulation and the transition to infant self-regulation. Metabolic mapping of 2deoxyglucose uptake during odor-shock conditioning in postnatal day (PN) 14 rat pups showed that maternal presence blocked fear learning, disengaged mesolimbic circuitry, basolateral amygdala (BLA), and plasticity-related AMPA receptor subunit trafficking. At PN18, when maternal presence only socially buffers threat learning (similar to social modulation in adults), maternal presence failed to disengage the mesolimbic dopaminergic system, and failed to disengage both the BLA and plasticity-related AMPA receptor subunit trafficking. Further, maternal presence failed to block threat learning at PN14 pups following abuse, and mesolimbic dopamine engagement and AMPA were not significantly altered by maternal presence-analogous to compromised maternal regulation of children in abusive relationships. Our results highlight three key features of maternal regulation: (1) maternal presence blocks fear learning and amygdala plasticity through age-dependent suppression of amygdala AMPA receptor subunit trafficking, (2) maternal presence suppresses engagement of brain regions within the mesolimbic dopamine circuit, and (3) early-life abuse compromises network and molecular biomarkers of maternal regulation, suggesting reduced social scaffolding of the brain.
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| 2. |
- Barr, Gordon A, et al.
(författare)
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Transitions in infant learning are modulated by dopamine in the amygdala
- 2009
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 12, s. 1367-1369
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Tidskriftsartikel (refereegranskat)abstract
- Behavioral transitions characterize development. Young infant rats paradoxically prefer odors that are paired with shock, but older pups learn aversions. This transition is amygdala and corticosterone dependent. Using microarrays and microdialysis, we found downregulated dopaminergic presynaptic function in the amygdala with preference learning. Corticosterone-injected 8-d-old pups and untreated 12-d-old pups learned aversions and had dopaminergic upregulation in the amygdala. Dopamine injection into the amygdala changed preferences to aversions, whereas dopamine antagonism reinstated preference learning.
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| 3. |
- Moriceau, Stephanie, et al.
(författare)
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Concurrent Neonatal Activation Of The Amygdala-fear Circuit And The Attachment Circuit During Infancy
- 2007
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Konferensbidrag (refereegranskat)abstract
- Infant altricial species learn to prefer stimuli paired with pain, presumably due to the importance of learning to prefer the caregiver regardless of the qual ity of care. This attenuated avoidance/fear learning appears due to low corticosterone (CORT), which keeps the amygdala ‘‘dormant’’. Indeed, simply increasing CORT permits amygdala plasticity and fear conditioning. Here we assess whether CORT also activates the locus coeruleus (LC) and increases NE via amygdala CRF efferents to the LC. In all experiments, PN7–8 pups received 11 pairings of odor-0.5 mA shock and were tested the next day for an odor preference/aversion (Y-maze). 14C 2-DG was used for neural assessment during conditioning. In Experiment 1, we found that the CORT induced odor aversion was correlated with olfactory bulb activation. Since this neural change is usually dependent upon increased NE and limited to neonates, we next assessed the pathway from the amygdala to the LC. In Experiment 2, we directly infused CORT into the lateral amygdala that activates the CRF efferents to the LC and an odor aversion was again obtained. In Experiment 3, we infused CRF directly into the LC, which produced an odor aversion and an increase in olfactory bulb NE (microdialysis). Pups with control LC vehicle infusions continued to acquire the age characteristic shock-induced odor preference. These results suggested that early activation of the amygdala dependent fear system can be precociously induce in neonates, although this is done in concert with the neonatal NE olfactory bulb learning system. [RMS Funding NSF IBN0117234, NICHD HD33402, OCAST]
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| 4. |
- Moriceau, Stephanie, et al.
(författare)
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Early-Life Stress Disrupts Attachment Learning : The Role of Amygdala Corticosterone, Locus Ceruleus Corticotropin Releasing Hormone, and Olfactory Bulb Norepinephrine
- 2009
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Ingår i: Journal of Neuroscience. - Washington, United States : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 29:50, s. 15745-15755
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Tidskriftsartikel (refereegranskat)abstract
- Infant rats require maternal odor learning to guide pups’ proximity-seeking of the mother and nursing. Maternal odor learning occurs using a simple learning circuit including robust olfactory bulb norepinephrine (NE), release from the locus ceruleus (LC), and amygdala suppression by low corticosterone (CORT). Early-life stress increases NE but also CORT, and we questioned whether early-life stress disrupted attachment learning and its neural correlates [2-deoxyglucose (2-DG) autoradiography]. Neonatal rats were normally reared or stressed-reared during the first 6 d of life by providing the mother with insufficient bedding for nest building and were odor–0.5 mA shock conditioned at 7 d old. Normally reared paired pups exhibited typical odor approach learning and associated olfactory bulb enhanced 2-DG uptake. However, stressed-reared pups showed odor avoidance learning and both olfactory bulb and amygdala 2-DG uptake enhancement. Furthermore, stressed-reared pups had elevated CORT levels, and systemic CORT antagonist injection reestablished the age-appropriate odor-preference learning, enhanced olfactory bulb, and attenuated amygdala 2-DG. We also assessed the neural mechanism for stressed-reared pups’ abnormal behavior in a more controlled environment by injecting normally reared pups with CORT. This was sufficient to produce odor aversion, as well as dual amygdala and olfactory bulb enhanced 2-DG uptake. Moreover, we assessed a unique cascade of neural events for the aberrant effects of stress rearing: the amygdala–LC–olfactory bulb pathway. Intra-amygdala CORT or intra-LC corticotropin releasing hormone (CRH) infusion supported aversion learning with intra-LC CRH infusion associated with increased olfactory bulb NE (microdialysis). These results suggest that early-life stress disturbs attachment behavior via a unique cascade of events (amygdala–LC–olfactory bulb).
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| 5. |
- Opendak, Maya, et al.
(författare)
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Adverse caregiving in infancy blunts neural processing of the mother
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The roots of psychopathology frequently take shape during infancy in the context of parent-infant interactions and adversity. Yet, neurobiological mechanisms linking these processes during infancy remain elusive. Here, using responses to attachment figures among infants who experienced adversity as a benchmark, we assessed rat pup cortical local field potentials (LFPs) and behaviors exposed to adversity in response to maternal rough and nurturing handling by examining its impact on pup separation-reunion with the mother. We show that during adversity, pup cortical LFP dynamic range decreased during nurturing maternal behaviors, but was minimally impacted by rough handling. During reunion, adversity-experiencing pups showed aberrant interactions with mother and blunted cortical LFP. Blocking pup stress hormone during either adversity or reunion restored typical behavior, LFP power, and cross-frequency coupling. This translational approach suggests adversity-rearing produces a stress-induced aberrant neurobehavioral processing of the mother, which can be used as an early biomarker of later-life pathology. The roots of psychopathology take shape during adverse parent-infant interactions, shown through infant attachment quality. Using rodents, the authors show that blunted infant cortical processing of the mother determines attachment quality through a stress hormone-dependent mechanism.
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| 6. |
- Raineki, Charlis, et al.
(författare)
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Ontogeny of odor-LiCl vs. odor-shock learning : Similar behaviors but divergent ages of functional amygdala emergence
- 2009
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Ingår i: Learning & memory (Cold Spring Harbor, N.Y.). - : Cold Spring Harbor Laboratory Press (CSHL). - 1072-0502 .- 1549-5485. ; 16:2, s. 114-121
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Tidskriftsartikel (refereegranskat)abstract
- Both odor-preference and odor-aversion learning occur in perinatal pups before the maturation of brain structures that support this learning in adults. To characterize the development of odor learning, we compared three learning paradigms: (1) odor-LiCl (0.3M; 1% body weight, ip) and (2) odor-1.2-mA shock (hindlimb, 1sec)ￜboth of which consistently produce odor-aversion learning throughout life and (3) odor-0.5-mA shock, which produces an odor preference in early life but an odor avoidance as pups mature. Pups were trained at postnatal day (PN) 7ￜ8, 12ￜ13, or 23ￜ24, using odor-LiCl and two odor-shock conditioning paradigms of odor-0.5-mA shock and odor-1.2-mA shock. Here we show that in the youngest pups (PN7ￜ8), odor-preference learning was associated with activity in the anterior piriform (olfactory) cortex, while odor-aversion learning was associated with activity in the posterior piriform cortex. At PN12ￜ13, when all conditioning paradigms produced an odor aversion, the odor-0.5-mA shock, odor-1.2-mA shock, and odor-LiCl all continued producing learning-associated changes in the posterior piriform cortex. However, only odor-0.5-mA shock induced learning-associated changes within the basolateral amygdala. At weaning (PN23ￜ24), all learning paradigms produced learning-associated changes in the posterior piriform cortex and basolateral amygdala complex. These results suggest at least two basic principles of the development of the neurobiology of learning: (1) Learning that appears similar throughout development can be supported by neural systems showing very robust developmental changes, and (2) the emergence of amygdala function depends on the learning protocol and reinforcement condition being assessed.
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| 7. |
- Rincon-Cortes, Millie, et al.
(författare)
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Enduring good memories of infant trauma: Rescue of adult neurobehavioral deficits via amygdala serotonin and corticosterone interaction
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:3, s. 881-886
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Tidskriftsartikel (refereegranskat)abstract
- Children form a strong attachment to their caregiver-even when that caretaker is abusive. Paradoxically, despite the trauma experienced within this relationship, the child develops a preference for trauma-linked cues-a phenomenon known as trauma bonding. Although infant trauma compromises neurobehavioral development, the mechanisms underlying the interaction between infant trauma bonding (i.e., learned preference for trauma cues) and the long-term effects of trauma (i.e., depressive-like behavior, amygdala dysfunction) are unknown. We modeled infant trauma bonding by using odor-shock conditioning in rat pups, which engages the attachment system and produces a life-long preference for the odor that was paired with shock. In adulthood, this trauma-linked odor rescues depressive-like behavior and amygdala dysfunction, reduces corticosterone (CORT) levels, and exerts repair-related changes at the molecular level. Amygdala microarray after rescue implicates serotonin (5-HT) and glucocorticoids (GCs), and a causal role was verified through microinfusions. Blocking amygdala 5-HT eliminates the rescue effect; increasing amygdala 5-HT and blocking systemic CORT mimics it. Our findings suggest that infant trauma cues share properties with antidepressants and safety signals and provide insight into mechanisms by which infant trauma memories remain powerful throughout life.
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| 8. |
- Robinson-Drummer, Patrese A., et al.
(författare)
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Infant Trauma Alters Social Buffering of Threat Learning : Emerging Role of Prefrontal Cortex in Preadolescence
- 2019
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Ingår i: Frontiers in Behavioral Neuroscience. - : Frontiers Media SA. - 1662-5153. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Within the infant-caregiver attachment system, the primary caregiver holds potent reward value to the infant, exhibited by infants' strong preference for approach responses and proximity-seeking towards the mother. A less well-understood feature of the attachment figure is the caregiver's ability to reduce fear via social buffering, commonly associated with the notion of a safe haven in the developmental literature. Evidence suggests this infant system overlaps with the neural network supporting social buffering (attenuation) of fear in the adults of many species, a network known to involve the prefrontal cortex (PFC). Here, using odor-shock conditioning in young developing rats, we assessed when the infant system transitions to the adult-like PFC-dependent social buffering of threat system. Rat pups were odor-shock conditioned (0.55 mA-0.6 mA) at either postnatal day (PN18; dependent on mother) or 28 (newly independent, weaned at PN23). Within each age group, the mother was present or absent during conditioning, with PFC assessment following acquisition using(14)C 2-DG autoradiography and cue testing the following day. Since the human literature suggests poor attachment attenuates the mother's ability to socially buffer the infants, half of the pups at each age were reared with an abusive mother from PN8-12. The results showed that for typical control rearing, the mother attenuated fear in both PN18 and PN28 pups, although the PFC [infralimbic (IL) and ventral prelimbic (vPL) cortices] was only engaged at PN28. Abuse rearing completely disrupted social buffering of pups by the mother at PN18. The results from PN28 pups showed that while the mother modulated learning in both control and abuse-reared pups, the behavioral and PFC effects were attenuated after maltreatment. Our data suggest that pups transition to the adult-like PFC social support circuit after independence from the mother (PN28), and this circuit remains functional after early-life trauma, although its effectiveness appears reduced. This is in sharp contrast to the effects of early life trauma during infancy, where social buffering of the infant is more robustly impacted. We suggest that the infant social buffering circuit is disengaged by early-life trauma, while the adolescent PFC-dependent social buffering circuit may use a safety signal with unreliable safety value.
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| 9. |
- Shionoya, Kiseko, 1964-, et al.
(författare)
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Development switch in neural circuitry underlying odor-malaise learning
- 2006
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Ingår i: Learning & memory (Cold Spring Harbor, N.Y.). - : Cold Spring Harbor Laboratory Press (CSHL). - 1072-0502 .- 1549-5485. ; 13:6, s. 801-808
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Tidskriftsartikel (refereegranskat)abstract
- Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and a 30-min peppermint-odor exposure. Conditioning groups included: Paired odor-LiCl, Paired odor-LiCl-Nursing, LiCl, and odor-saline. Results showed that Paired LiCl-odor conditioning induced a learned odor aversion in postnatal day (PN) 7, 12, and 23 pups. Odor-LiCl Paired Nursing induced a learned odor preference in PN7 and PN12 pups but blocked learning in PN23 pups. 14C 2-deoxyglucose (2-DG) autoradiography indicated enhanced olfactory bulb activity in PN7 and PN12 pups with odor preference and avoidance learning. The odor aversion in weanling aged (PN23) pups resulted in enhanced amygdala activity in Paired odor-LiCl pups, but not if they were nursing. Thus, the neural circuit supporting malaise-induced aversions changes over development, indicating that similar infant and adult-learned behaviors may have distinct neural circuits.
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| 10. |
- Shionoya, Kiseko, 1964-, et al.
(författare)
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Maternal attenuation of hypothalamic paraventricular nucleus norepinephrine switches avoidance learning to preference learning in preweanling rat pups
- 2007
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Ingår i: Hormones and Behavior. - : Elsevier. - 0018-506X .- 1095-6867. ; 52:3, s. 391-400
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Tidskriftsartikel (refereegranskat)abstract
- Infant rats learn to prefer stimuli paired with pain, presumably due to the importance of learning to prefer the caregiver to receive protection and food. With maturity, a more ‘adult-like’ learning system emerges that includes the amygdala and avoidance/fear learning. The attachment and ‘adult-like’ systems appear to co-exist in older pups with maternal presence engaging the attachment system by lowering corticosterone (CORT). Specifically, odor–shock conditioning (11 odor–0.5 mA shock trials) in 12-day-old pups results in an odor aversion, although an odor preference is learned if the mother is present during conditioning. Here, we propose a mechanism to explain pups ability to ‘switch’ between the dual learning systems by exploring the effect of maternal presence on hypothalamic paraventricular nucleus (PVN) neural activity, norepinephrine (NE) levels and learning. Maternal presence attenuates both PVN neural activity and PVN NE levels during odor–shock conditioning. Intra-PVN NE receptor antagonist infusion blocked the odor aversion learning with maternal absence, while intra-PVN NE receptor agonist infusion permitted odor aversion learning with maternal presence. These data suggest maternal control over pup learning acts through attenuation of PVN NE to reduce the CORT required for pup odor aversion learning. Moreover, these data also represent pups’ continued maternal dependence for nursing, while enabling aversion learning outside the nest to prepare for pups future independent living.
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| 11. |
- Smith, Jonathan J., et al.
(författare)
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Auditory Stimulation Dishabituates Olfactory Responses via Noradrenergic Cortical Modulation
- 2009
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Ingår i: Neural Plasticity. - : Hindawi Publishing Corporation. - 2090-5904 .- 1687-5443. ; 2009
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Tidskriftsartikel (refereegranskat)abstract
- Dishabituation is a return of a habituated response if context or contingency changes. In the mammalian olfactory system, metabotropic glutamate receptor mediated synaptic depression of cortical afferents underlies short-term habituation to odors. It was hypothesized that a known antagonistic interaction between these receptors and norepinephrine -receptors provides a mechanism for dishabituation. The results demonstrate that a 108 dB siren induces a two-fold increase in norepinephrine content in the piriform cortex. The same auditory stimulus induces dishabituation of odor-evoked heart rate orienting bradycardia responses in awake rats. Finally, blockade of piriform cortical norepinephrine -receptors with bilateral intracortical infusions of propranolol (100 M) disrupts auditory-induced dishabituation of odor-evoked bradycardia responses. These results provide a cortical mechanism for a return of habituated sensory responses following a cross-modal alerting stimulus.
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| 12. |
- Sullivan, Regina M., et al.
(författare)
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Developmental Neurobiology of Olfactory Preference and Avoidance Learning
- 2014
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Ingår i: Oxford Handbook of Developmental Behavioral Neuroscience. - Oxford : Oxford University Press. - 9780195314731 ; , s. 573-587
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Infants from a myriad of species attach to their caregiver regardless of the quality of care received, although the quality of care influences development of the stress system. To better understand this relationship, this chapter characterizes attachment learning and the supporting neural circuit in infant rat pups. During early life, odors paired with pain paradoxically produce subsequent approach responses to the odor and attachment. The neural circuit supporting this attachment learning involves the olfactory bulb encoding the preference learning and suppression of the amygdala to prevent the aversion learning. Increasing the stress hormone corticosterone during acquisition or decreasing endogenous opioids during consolidation prevents this odor approach learning. These data suggest that early life attachment is readily learned and supported by both increased opioids and decreased stress.
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