Maternal Odor Research Articles

Neurobehavioral assessment of maternal odor in developing rat pups: implications for social buffering

ABSTRACTSocial support can attenuate the behavioral and stress hormone response to threat, a phenomenon called social buffering. The mother’s social buffering of the infant is one of the more robust examples; yet we understand little about the neurobiology. Using a rodent model, we explore the neurobiology of social buffering by assessing neural processing of the maternal odor, a major cue controlling social buffering in rat pups. We used pups before (postnatal day (PN) 7) and after (PN14, PN23) the functional emergence of social buffering. Pups were injected with 14C 2-deoxyglucose (2-DG) and presented with the maternal odor, a control preferred odor incapable of social buffering (acetophenone), or no odor. Brains were removed, processed for autoradiography and brain areas identified as important in adult social buffering were assessed, including the amygdala basolateral complex (Basolateral Amygdala [BLA]), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC). Results suggest dramatic changes in the processing of maternal odor. PN7 pups show mPFC and ACC activation, although PN14 pups showed no activation of the mPFC, ACC, or BLA. All brain areas assessed were recruited by PN23. Additional analysis suggests substantial changes in functional connectivity across development. Together, these results imply complex nonlinear transitions in the neurobiology of social buffering in early life that may provide insight into the changing role of the mother in supporting social buffering.

Effect of social odor context on the emission of isolation-induced ultrasonic vocalizations in the BTBR T+tf/J mouse model for autism.

An important diagnostic criterion for social communication deficits in autism spectrum disorders (ASD) are difficulties in adjusting behavior to suit different social contexts. While the BTBR T+tf/J (BTBR) inbred strain of mice is one of the most commonly used mouse models for ASD, little is known about whether BTBR mice display deficits in detecting changes in social context and their ability to adjust to them. Here, it was tested therefore whether the emission of isolation-induced ultrasonic vocalizations (USV) in BTBR mouse pups is affected by the social odor context, in comparison to the standard control strain with high sociability, C57BL/6J (B6). It is known that the presence of odors from mothers and littermates leads to a calming of the isolated mouse pup, and hence to a reduction in isolation-induced USV emission. In accordance with their behavioral phenotypes with relevance to all diagnostic core symptoms of ASD, it was predicted that BTBR mouse pups would not display a calming response when tested under soiled bedding conditions with home cage bedding material containing maternal odors, and that similar isolation-induced USV emission rates would be seen in BTBR mice tested under clean and soiled bedding conditions. Unexpectedly, however, the present findings show that BTBR mouse pups display such a calming response and emit fewer isolation-induced USV when tested under soiled as compared to clean bedding conditions, similar to B6 mouse pups. Yet, in contrast to B6 mouse pups, which emitted isolation-induced USV with shorter call durations and lower levels of frequency modulation under soiled bedding conditions, social odor context had no effect on acoustic call features in BTBR mouse pups. This indicates that the BTBR mouse model for ASD does not display deficits in detecting changes in social context, but has a limited ability and/or reduced motivation to adjust to them.

Pre-reproductive maternal enrichment influences rat maternal care and offspring developmental trajectories: behavioral performances and neuroplasticity correlates.

Environmental enrichment (EE) is a widely used paradigm for investigating the influence of complex stimulations on brain and behavior. Here we examined whether pre-reproductive exposure to EE of female rats may influence their maternal care and offspring cognitive performances. To this aim, from weaning to breeding age enriched females (EF) were reared in enriched environments. Females reared in standard conditions were used as controls. At 2.5 months of age all females were mated and reared in standard conditions with their offspring. Maternal care behaviors and nesting activity were assessed in lactating dams. Their male pups were also behaviorally evaluated at different post-natal days (pnd). Brain BDNF, reelin and adult hippocampal neurogenesis levels were measured as biochemical correlates of neuroplasticity. EF showed more complex maternal care than controls due to their higher levels of licking, crouching and nest building activities. Moreover, their offspring showed higher discriminative (maternal odor preference T-maze, pnd 10) and spatial (Morris Water Maze, pnd 45; Open Field with objects, pnd 55) performances, with no differences in social abilities (Sociability test, pnd 35), in comparison to controls. BDNF levels were increased in EF frontal cortex at pups' weaning and in their offspring hippocampus at pnd 21 and 55. No differences in offspring reelin and adult hippocampal neurogenesis levels were found. In conclusion, our study indicates that pre-reproductive maternal enrichment positively influences female rats' maternal care and cognitive development of their offspring, demonstrating thus a transgenerational transmission of EE benefits linked to enhanced BDNF-induced neuroplasticity.

Why Do Children Wish to Stay with Their Abusers? A Translational Study

Abused children often choose, counterintuitively, to stay with their abusing parents even during court proceedings offering placement outside the home. To study the pathophysiology of this phenomenon, investigators used an animal model in which infant rats are introduced to and bond with a peppermint odor (an established substitute for maternal odor) …

Paradoxical neurobehavioral rescue by memories of early-life abuse: the safety signal value of odors learned during abusive attachment.

Caregiver-associated cues, including those learned in abusive attachment, provide a sense of safety and security to the child. Here, we explore how cues associated with abusive attachment, such as maternal odor, can modify the enduring neurobehavioral effects of early-life abuse. Two early-life abuse models were used: a naturalistic paradigm, where rat pups were reared by an abusive mother; and a more controlled paradigm, where pups underwent peppermint odor-shock conditioning that produces an artificial maternal odor through engagement of the attachment circuit. Animals were tested for maternal odor preference in infancy, forced swim test (FST), social behavior, and sexual motivation in adulthood-in the presence or absence of maternal odors (natural or peppermint). Amygdala odor-evoked local field potentials (LFPs) via wireless electrodes were also examined in response to the maternal odors in adulthood. Both early-life abuse models induced preference for the maternal odors in infancy. In adulthood, these early-life abuse models produced FST deficits and decreased social behavior, but did not change sexual motivation. Presentation of the maternal odors rescued FST and social behavior deficits induced by early-life abuse and enhanced sexual motivation in all animals. In addition, amygdala LFPs from both abuse animal models showed unique activation within the gamma frequency (70-90 Hz) bands in response to the specific maternal odor present during early-life abuse. These results suggest that attachment-related cues learned during infancy have a profound ability to rescue neurobehavioral dysregulation caused by early-life abuse. Paradoxically, abuse-associated cues seem to acquire powerful and enduring antidepressive properties and alter amygdala modulation.

PO-0458 Full-term Newborns Detect Maternal Breast Odours At A Cortical Level: A Multichannel Nirs Study

Background and aims Behavioural and physiological changes have been recorded in newborns following exposure to maternal odours. We aimed to investigate the cortical activation following the presentation of maternal breast odours (MBO). Methods We used a multichannel NIRS device to record bilaterally cortical activation in the orbito-frontal gyri (OFG), prefrontal (PFC) and primary somatosensory (S1) cortices during 50 s (10 s baseline, 10 s presentation, 30 s post-stimuli). Odours were presented in controlled conditions (silent room, active sleep, randomised order) using cotton cloths: clean (CC) and worn by the mother in her bra during preceding 12 h (MBO). Seventeen full-term infants were included. After systematic artefact removal HbO 2 changes from baseline and between odours were compared using ANOVA and post-hoc analysis. Results We found no S1 activation following any odour. MBO (and not CC) induced an increase bilaterally in the OFG (p > 0,001). MBO as compared to CC elicited a higher increase (p The mean increase of HbO 2 from baseline during the 30 s post stimuli were higher in MBO as compared to CC: · 3,3 (0,7–5,9) μmol/l vs 0,8 (-1,4–3,0) μmol/l in the left OFG. · 2,4 (-0,3–5,2) μmol/l vs 1,1 (-1,2–3,4) μmol/l in the right OFG. Conclusions Newborn infants can detect their MBO at a cortical level and discriminate it from a control smell. As MBO is used in the NICU it is of great interest to further investigate how hospitalised infants react cortically to MBO.

Facilitation of action planning in children with autism: The contribution of the maternal body odor

Imitation is a key socio-cognitive skill impaired in individuals with Autism Spectrum Conditions (ASC). It is known that the familiarity with an actor facilitates the appearance of imitative abilities. Here, we explore whether a highly familiar and socially relevant stimulus presented in the olfactory modality is able to improve spontaneous imitation as early as at the level of action planning. A group of 20 children with ASC and 20 controls observed their own mother or the mother of another child performing a reach-to-grasp action towards an object, under the exposure to their maternal odor, the odor of the mother of another child or no odor. Subsequently, children acted upon the same object with no specific instruction to imitate. Child’s movement initiation time (MIT) served as an indicator of motor planning facilitation induced by action observation. Results suggest that for children with ASC (but not controls) MIT was significantly lower when exposed to the maternal odor both when interacting with a familiar or an unfamiliar model. In the former case, the performance is comparable to controls. The familiar model in the absence of any olfactory cue is able to induce a facilitation effect, but the maximal facilitation on MIT is evident when maternal odor and familiar model are paired. We hypothesize that for children with ASC the maternal odor provides relevant social motivation for taking advantage of others’ actions when planning movements in an imitative context.

Neurobiology of attachment to an abusive caregiver: short-term benefits and long-term costs.

Childhood maltreatment is associated with adverse brain development and later life psychiatric disorders, with maltreatment from the caregiver inducing a particular vulnerability to later life psychopathologies. Here we review two complementary rodent models of early life abuse, which are used to examine the infant response to trauma within attachment and the developmental trajectories that lead to later life neurobehavioral deficits. These rodent models include being reared with an abusive mother, and a more controlled attachment-learning paradigm using odor-shock conditioning to produce a new maternal odor. In both of these rodent models, pups learn a strong attachment and preference to the maternal odor. However, both models produce similar enduring neurobehavioral deficits, which emerge with maturation. Importantly, cues associated with our models of abuse serve as paradoxical safety signals, by normalizing enduring neurobehavioral deficits following abuse. Here we review these models and explore implications for human interventions for early life maltreatment.

Early Life Trauma and Attachment: Immediate and Enduring Effects on Neurobehavioral and Stress Axis Development

Over half a century of converging clinical and animal research indicates that early life experiences induce enduring neuroplasticity of the HPA-axis and the developing brain. This experience-induced neuroplasticity is due to alterations in the frequency and intensity of stimulation of pups’ sensory systems (i.e., olfactory, somatosensory, gustatory) embedded in mother–infant interactions. This stimulation provides “hidden regulators” of pups’ behavioral, physiological, and neural responses that have both immediate and enduring consequences, including those involving the stress response. While variation in stimulation can produce individual differences and adaptive behaviors, pathological early life experiences can induce maladaptive behaviors, initiate a pathway to pathology, and increase risk for later-life psychopathologies, such as mood and affective disorders, suggesting that infant-attachment relationships program later-life neurobehavioral function. Recent evidence suggests that the effects of maternal presence or absence during this sensory stimulation provide a major modulatory role in neural and endocrine system responses, which have minimal impact on pups’ immediate neurobehavior but a robust impact on neurobehavioral development. This concept is reviewed here using two complementary rodent models of infant trauma within attachment: infant paired-odor-shock conditioning (mimicking maternal odor attachment learning) and rearing with an abusive mother that converge in producing a similar behavioral phenotype in later-life including depressive-like behavior as well as disrupted HPA-axis and amygdala function. The importance of maternal social presence on pups’ immediate and enduring brain and behavior suggests unique processing of sensory stimuli in early life that could provide insight into the development of novel strategies for prevention and therapeutic interventions for trauma experienced with the abusive caregiver.

Gestational methyl donor deficiency alters key proteins involved in neurosteroidogenesis in the olfactory bulbs of newborn female rats and is associated with impaired olfactory performance

Gestational methyl donor deficiency (MDD) leads to growth retardation as well as to cognitive and motor disorders in 21-d-old rat pups. These disorders are related to impaired neurogenesis in the cerebral neurogenic areas. Olfactory bulbs (OB), the main target of neuronal progenitors originating from the subventricular zone, play a critical role during the postnatal period by allowing the pups to identify maternal odour. We hypothesised that growth retardation could result from impaired suckling due to impaired olfactory discrimination through imbalanced apoptosis/neurogenesis in the OB. Since neurosteroidogenesis modulates neurogenesis in OB, in the present study, we investigated whether altered neurosteroidogenesis could explain some these effects. Pups born to dams fed a normal diet (n 24) and a MDD diet (n 27) were subjected to olfactory tests during the lactation and weaning periods (n 24 and 20, respectively). We studied the markers of apoptosis/neurogenesis and the expression levels of the key neurosteroidogenic enzyme aromatase, the cholesterol-transfer protein StAR (steroidogenic acute regulatory protein) and the ERα oestrogen receptor and the content of oestradiol in OB. The 21-d-old MDD female pups displayed lower body weight and impaired olfactory discrimination when compared with the control pups. MDD led to greater homocysteine accumulation and more pronounced apoptosis, along with impaired cell proliferation in the OB of female pups. The expression levels of aromatase, StAR and ERα as well as the content of oestradiol were lower in the OB of the MDD female pups than in those of the control female pups. In conclusion, gestational MDD may alter olfactory discrimination performances by affecting neurogenesis, apoptosis and neurosteroidogenesis in OB in a sex-dependent manner. It may be involved in growth retardation through impaired suckling.

Body Odors Promote Automatic Imitation in Autism

Autism spectrum disorders comprise a range of neurodevelopmental pathologies characterized, among other symptoms, by impaired social interactions. Individuals with this diagnosis are reported to often identify people by repetitively sniffing pieces of clothing or the body odor of family members. Since body odors are known to initiate and mediate many different social behaviors, smelling the body odor of a family member might constitute a sensory-based action promoting social contact. In light of this, we hypothesized that the body odor of a family member would facilitate the appearance of automatic imitation, an essential social skill known to be impaired in autism. We recruited 20 autistic and 20 typically developing children. Body odors were collected from the children's mothers' axillae. A child observed a model (their mother or a stranger mother) execute (or not) a reach-to-grasp action toward an object. Subsequently, she performed the same action. The object was imbued with the child's mother's odor, a stranger mother's odor, or no odor. The actions were videotaped, and movement time was calculated post hoc via a digitalization technique. Automatic imitation effects-expressed in terms of total movement time reduction-appear in autistic children only when exposed to objects paired with their own mother's odor. The maternal odor, which conveys a social message otherwise neglected, helps autistic children to covertly imitate the actions of others. Our results represent a starting point holding theoretical and practical relevance for the development of new strategies to enhance communication and social behavior among autistic individuals.

Prenatal lipopolysaccharide increases maternal behavior, decreases maternal odor preference, and induces lipopolysaccharide hyporesponsiveness.

The present study investigated whether late maternal inflammation disrupts the mother/pup interaction, resulting in long-lasting effects on pup behavior and alterations in biological pathways, thereby programming prepubertal behavior and the pups' inflammatory responses after bacterial endotoxin treatment. Female rats received 100 μg/kg lipopolysaccharide (LPS) or .9% saline solution on gestation day 18. Reproductive performance was observed at birth. On lactation days (LD) 5 and LD 6, respectively, maternal behavior and maternal aggressive behavior were assessed. In pups, maternal odor preference on LD 7, open field behavior on LD 21, and serum tumor necrosis factor α (TNF-α) levels after LPS challenge on LD 21 were investigated. The results showed that prenatal LPS exposure improved maternal care and reduced maternal aggressive behavior but did not alter maternal reproductive performance. Male offspring exhibited increased body weights at birth and reduced maternal odor preference. Lipopolysaccharide challenge increased the duration of immobility in the open field and induced a slight increase in serum TNF-α levels. Prenatal exposure to LPS during late pregnancy improved maternal care, reduced maternal olfactory preference, and induced TNF-α hyporesponsiveness to a single dose of LPS in pups.

Early survival factor deprivation in the olfactory epithelium enhances activity-driven survival

The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs). However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226). We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population toward detection of environmental odorants.

Neonatal handling induces deficits in infant mother preference and adult partner preference

Neonatal handling is an experimental procedure used to understand how early-life adversity can negatively affect neurobehavioral development and place animals on a pathway to pathology. Decreased preference for the maternal odor during infancy is one of many behavioral deficits induced by neonatal handling. Here, we hypothesize that deficits in maternal odor preference may interfere with partner preference in the adult. To test this hypothesis, we assessed infant maternal odor preference and adult partner preference in different reproductive stages in both male and female rats that received neonatal handling. Our results indicate that only neonatally handled females present deficits in maternal odor preference during infancy, but both male and females present deficits in adult partner preference. However, sexual experience was effective in rescuing partner preference deficits in males. These results indicate that, considering infant and adult social interactions, females are more susceptible to the effects of neonatal handling than males.

Developmental Neurobiology of the Rat Attachment System and Its Modulation by Stress

Stress is a powerful modulator of brain structure and function. While stress is beneficial for survival, inappropriate stress dramatically increases the risk of physical and mental health problems, particularly when experienced during early developmental periods. Here we focus on the neurobiology of the infant rat’s odor learning system that enables neonates to learn and approach the maternal odor and describe the unique role of the stress hormone corticosterone in modulating this odor approach learning across development. During the first nine postnatal days, this odor approach learning of infant rats is supported by a wide range of sensory stimuli and ensures attachment to the mother’s odor, even when interactions with her are occasionally associated with pain. With maturation and the emergence of a stress- or pain-induced corticosterone response, this odor approach learning terminates and a more adult-like amygdala-dependent fear/avoidance learning emerges. Strikingly, the odor approach and attenuated fear learning of older pups can be re-established by the presence of the mother, due to her ability to suppress her pups’ corticosterone release and amygdala activity. This suggests that developmental changes in stress responsiveness and the stimuli that produce a stress response might be critically involved in optimally adapting the pup’s attachment system to its respective ecological niche.

Maternal Contact Differentially Modulates Central and Peripheral Oxytocin in Rat Pups During a Brief Regime of Mother–Pup Interaction that Induces a Filial Huddling Preference

Central oxytocin mediates the acquisition of a filial preference for maternal odour in rat pups, manifested by their huddling preferences. The present study was designed to examine whether maternal care modulates oxytocin concentrations in rat pups and, if so, how different types of maternal contact are associated with the pups' oxytocin concentrations. Pairs of 14-day-old littermates were removed from their home cage for 1 h and then placed with a lactating foster mother for 2 h, or they remained isolated at room temperature. Enzyme immunoassays revealed that maternal care and maternal separation can differentially modulate pups' oxytocin concentrations. Both hypothalamic and serum oxytocin increased during the 1-h separation. Pups placed with a foster mother after the separation maintained the same concentrations in the hypothalamus and serum through the fostering period. By contrast, pups placed with no mother showed a further increase in hypothalamic oxytocin but serum oxytocin decreased. Behavioural analyses revealed that skin-to-skin contact with the mother, but not simple physical contact or maternal licking/grooming, was positively correlated with the pups' hypothalamic oxytocin concentrations. These neuroendocrine data match previous findings showing that skin-to-skin contact with mother facilitates the acquisition of the pups' huddling preference for a maternally-associated odour. Taken together, the present study suggests that maternal skin-to-skin contact stimulates pups' central oxytocin, at the same time as creating the conditions for inducing a preference for maternal odour and establishing a social affiliation in rat pups; the natural schedule of maternal separation and reunion may modulate pups' oxytocin concentrations, providing scaffolding for the acquisition of their filial huddling preference.

Role of maternal odors on foraging behavior during postnatal development in a solitary subterranean rodent Ctenomys talarum

We investigated the role of maternal odors emanating from excretory deposits and/or glandular secretions during the postnatal development of foraging and related behaviors in young Los Talas’ tuco-tucos (Ctenomys talarum), a solitary rodent, under seminatural conditions. During cafeteria tests, we offered them two of the grasses most preferred by adults of this species (bromegrass, Bromus unioloides and panicgrass, Panicum racemosum). We scent marked one dietary option in a treatment group, and the other option in a second treatment group, keeping a third group with no odors as control. Pups did not show to prefer a special grass in particular, and maternal odors showed no effect on the behavioral variables evaluated in this study. When they reached their weaning age, they showed an ontogenetic change in food preferences, where they preferred bromegrass, and maternal odors influenced negatively on the consumption of panicgrass. During dispersal, preference for bromegrass was expressed independently of the presence of maternal odors. Overall, their effect was less pronounced than age’s effect, and it was evident in only a subset of the conducted experiments. This study shows that the influence of maternal odors is not essential for the establishment of feeding or site preferences in this species in seminatural conditions, contrarily to what was observed in other studies performed with social mammal species (i.e., rats and rabbits). It is suggested that other factors (e.g., individual learning) might influence the observed preferences.

Prenatal LPS exposure reduces olfactory perception in neonatal and adult rats

Prenatal lipopolysaccharide (LPS) exposure causes reproductive, behavioral and neurochemical defects in both dams and pups. The present study evaluated male rats prenatally treated with LPS for behavioral and neurological effects related to the olfactory system, which is the main sensorial path in rodents. Pregnant Wistar rats received 100μg/kg of LPS intraperitoneally (i.p.) on gestational day (GD) 9.5, and maternal behavior was evaluated. Pups were evaluated for (1) maternal odor preference, (2) aversion to cat odor, (3) monoamine levels and turnover in the olfactory bulb (OB) and (4) protein expression (via immunoblotting) within the OB dopaminergic system and glial cells. Results showed that prenatal LPS exposure impaired maternal preference and cat odor aversion and decreased dopamine (DA) levels in the OB. This dopaminergic impairment may have been due to defects in another brain area given that protein expression of the first enzyme in the DA biosynthetic pathway was unchanged in the OB. Moreover, there was no change in the protein expression of the DA receptors. The fact that the number of astrocytes and microglia was not increased suggests that prenatal LPS did not induce neuroinflammation in the OB. Furthermore, given that maternal care was not impaired, abnormalities in the offspring were not the result of reduced maternal care.

The neurobiology of infant maternal odor learning

Infant rats must learn to identify their mother's diet-dependent odor. Once learned, maternal odor controls pups' approach to the mother, their social behavior and nipple attachment. Here we present a review of the research from four different laboratories, which suggests that neural and behavioral responses to the natural maternal odor and neonatal learned odors are similar. Together, these data indicate that pups have a unique learning circuit relying on the olfactory bulb for neural plasticity and on the hyperfunctioning noradrenergic locus coeruleus flooding the olfactory bulb with norepinephrine to support the neural changes. Another important factor making this system unique is the inability of the amygdala to become incorporated into the infant learning circuit. Thus, infant rats appear to be primed in early life to learn odors that will evoke approach responses supporting attachment to the caregiver.

Adult depression-like behavior, amygdala and olfactory cortex functions are restored by odor previously paired with shock during infant's sensitive period attachment learning

Maltreatment from the caregiver induces vulnerability to later life psychopathologies, yet attraction and comfort is sometimes provided by cues associated with early life maltreatment. We used a rat model of early life maltreatment with odor–0.5 mA shock conditioning to produce depressive-like behaviors and questioned whether stimuli associated with maltreatment would restore emotional neurobehavioral function to control levels. Pups received daily novel odor–0.5 mA shock conditioning from postnatal day 8 to 12. This procedure produces a new maternal odor that controls pups’ attachment behaviors. In adulthood, either with or without the infant odor, animals received a Forced Swim Test, Sucrose Preference Test or assessment of amygdala and olfactory system functioning using field potential signal evoked by olfactory bulb paired-pulse electrical stimulation. Following neonatal odor–shock pairings, but not unpaired controls, adults without the odor present showed increased depression-like behavior in the Forced Swim Test and Sucrose Preference Test and a deficit in paired-pulse inhibition in amygdala and piriform (olfactory) cortex. All effects were brought to control levels when the infant conditioned odor was presented during behavioral and neural tests. The ability of cues associated with early life maltreatment to normalize behavior and amygdala activity suggests these cues provide adaptive value in adulthood.