The Neurobiology of Safety and Threat Learning in Infancy

Developmental Neuroscience, 2012

and begin to travel in and out of the nest, the specialized attachment learning becomes contextually confined to when pups are with the mother. Thus, when outside the nest, these older pups show learning more typical of adult learning, presumably to prepare for independent life outside the nest. The quality of attachment can alter this circuitry, with early life stress prematurely terminating the pups' access to the attachment system through premature functional activation of the amygdala. Overall, the attachment circuit appears to have a dual function: to keep pups close to the caregiver but also to shape pups' behavior to match the environment and define long-term emotion and cognition.

Genes, Brain and Behavior, 2013

Attachment to an abusive caregiver has wide phylogenetic representation, suggesting that animal models are useful in understanding the neural basis underlying this phenomenon and subsequent behavioral outcomes. We previously developed a rat model, in which we use classical conditioning to parallel learning processes evoked during secure attachment (odor-stroke, with stroke mimicking tactile stimulation from the caregiver) or attachment despite adversity (odor-shock, with shock mimicking maltreatment). Here we extend this model to mice. We conditioned infant mice (postnatal day (PN) 7-9 or 13-14) with presentations of peppermint odor and either stroking or shock. We used 14 C 2-deoxyglucose (2-DG) to assess olfactory bulb and amygdala metabolic changes following learning. PN7-9 mice learned to prefer an odor following either odor-stroke or shock conditioning, whereas odor-shock conditioning at PN13-14 resulted in aversion/fear learning. 2-DG data indicated enhanced bulbar activity in PN7-9 preference learning, whereas significant amygdala activity was present following aversion learning at PN13-14. Overall, the mouse results parallel behavioral and neural results in the rat model of attachment, and provide the foundation for the use of transgenic and knockout models to assess the impact of both genetic (biological vulnerabilities) and environmental factors (abusive) on attachment-related behaviors and behavioral development.

Emotional trauma is transmitted across generations. For example, children witnessing their parent expressing fear to specific sounds or images begin to express fear to those cues. Within normal range, this is adaptive, although pathological fear, such as occurs in posttraumatic stress disorder or specific phobias, is also socially transmitted to children and is thus of clinical concern. Here, using a rodent model, we report a mother-to-infant transfer of fear to a novel peppermint odor, which is dependent on the mother expressing fear to that smell in pups' presence. Examination of pups' neural activity using c-Fos early gene expression and 14 C 2-deoxyglucose autoradiography during mother-to-infant fear transmission revealed lateral and basal amygdala nuclei activity, with a causal role highlighted by pharmacological inactivation of pups' amygdala preventing the fear transmission. Maternal presence was not needed for fear transmission, because an elevation of pups' corticosterone induced by the odor of the frightened mother along with a novel peppermint odor was sufficient to produce pups' subsequent aversion to that odor. Disruption of axonal tracts from the Grueneberg ganglion, a structure implicated in alarm chemosignaling, or blockade of pups' alarm odor-induced corticosterone increase prevented transfer of fear. These memories are acquired at younger ages compared with amygdala-dependent odorshock conditioning and are more enduring following minimal conditioning. Our results provide clues to understanding transmission of specific fears across generations and its dependence upon maternal induction of pups' stress response paired with the cue to induce amygdala-dependent learning plasticity. Results are discussed within the context of caregiver emotional responses and adaptive vs. pathological fears social transmission. necklace glomeruli | pheromone | olfaction | PTSD | social referencing

Emotional trauma is transmitted across generations. For example, children witnessing their parent expressing fear to specific sounds or images begin to express fear to those cues. Within normal range, this is adaptive, although pathological fear, such as occurs in posttraumatic stress disorder or specific phobias, is also socially transmitted to children and is thus of clinical concern. Here, using a rodent model, we report a mother-to-infant transfer of fear to a novel peppermint odor, which is dependent on the mother expressing fear to that smell in pups' presence. Examination of pups' neural activity using c-Fos early gene expression and 14 C 2-deoxyglucose autoradiography during mother-to-infant fear transmission revealed lateral and basal amygdala nuclei activity, with a causal role highlighted by pharmacological inactivation of pups' amygdala preventing the fear transmission. Maternal presence was not needed for fear transmission, because an elevation of pups' corticosterone induced by the odor of the frightened mother along with a novel peppermint odor was sufficient to produce pups' subsequent aversion to that odor. Disruption of axonal tracts from the Grueneberg ganglion, a structure implicated in alarm chemosignaling, or blockade of pups' alarm odor-induced corticosterone increase prevented transfer of fear. These memories are acquired at younger ages compared with amygdala-dependent odorshock conditioning and are more enduring following minimal conditioning. Our results provide clues to understanding transmission of specific fears across generations and its dependence upon maternal induction of pups' stress response paired with the cue to induce amygdala-dependent learning plasticity. Results are discussed within the context of caregiver emotional responses and adaptive vs. pathological fears social transmission. necklace glomeruli | pheromone | olfaction | PTSD | social referencing

Proceedings of the National Academy of Sciences, 1998

The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly ( i ) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, ( ii ) increased α 2 adrenoreceptor density in the locus ceruleus, and ( iii ) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus. The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus ceruleus to th...

Emotional trauma is transmitted across generations. For example, children witnessing their parent expressing fear to specific sounds or images begin to express fear to those cues. Within normal range, this is adaptive, although pathological fear, such as occurs in posttraumatic stress disorder or specific phobias, is also socially transmitted to children and is thus of clinical concern. Here, using a rodent model, we report a mother-to-infant transfer of fear to a novel peppermint odor, which is dependent on the mother expressing fear to that smell in pups' presence. Examination of pups' neural activity using c-Fos early gene expression and 14 C 2-deoxyglucose autoradiography during mother-to-infant fear transmission revealed lateral and basal amygdala nuclei activity, with a causal role highlighted by pharmacological inactivation of pups' amygdala preventing the fear transmission. Maternal presence was not needed for fear transmission, because an elevation of pups' corticosterone induced by the odor of the frightened mother along with a novel peppermint odor was sufficient to produce pups' subsequent aversion to that odor. Disruption of axonal tracts from the Grueneberg ganglion, a structure implicated in alarm chemosignaling, or blockade of pups' alarm odor-induced corticosterone increase prevented transfer of fear. These memories are acquired at younger ages compared with amygdala-dependent odorshock conditioning and are more enduring following minimal conditioning. Our results provide clues to understanding transmission of specific fears across generations and its dependence upon maternal induction of pups' stress response paired with the cue to induce amygdala-dependent learning plasticity. Results are discussed within the context of caregiver emotional responses and adaptive vs. pathological fears social transmission. necklace glomeruli | pheromone | olfaction | PTSD | social referencing

Emotional trauma is transmitted across generations. For example, children witnessing their parent expressing fear to specific sounds or images begin to express fear to those cues. Within normal range, this is adaptive, although pathological fear, such as occurs in posttraumatic stress disorder or specific phobias, is also socially transmitted to children and is thus of clinical concern. Here, using a rodent model, we report a mother-to-infant transfer of fear to a novel peppermint odor, which is dependent on the mother expressing fear to that smell in pups' presence. Examination of pups' neural activity using c-Fos early gene expression and 14 C 2-deoxyglucose autoradiography during mother-to-infant fear transmission revealed lateral and basal amygdala nuclei activity, with a causal role highlighted by pharmacological inactivation of pups' amygdala preventing the fear transmission. Maternal presence was not needed for fear transmission, because an elevation of pups' corticosterone induced by the odor of the frightened mother along with a novel peppermint odor was sufficient to produce pups' subsequent aversion to that odor. Disruption of axonal tracts from the Grueneberg ganglion, a structure implicated in alarm chemosignaling, or blockade of pups' alarm odor-induced corticosterone increase prevented transfer of fear. These memories are acquired at younger ages compared with amygdala-dependent odorshock conditioning and are more enduring following minimal conditioning. Our results provide clues to understanding transmission of specific fears across generations and its dependence upon maternal induction of pups' stress response paired with the cue to induce amygdala-dependent learning plasticity. Results are discussed within the context of caregiver emotional responses and adaptive vs. pathological fears social transmission. necklace glomeruli | pheromone | olfaction | PTSD | social referencing

Developmental Psychobiology, 2005

A strong attachment to the caregiver is critical for survival in altricial species, including humans. While some behavioral aspects of attachment have been characterized, its neurobiology has only recently received attention. Using a mammalian imprinting model, we are assessing the neural circuitry that enables infant rats to attach quickly to a caregiver, thus enhancing survival in the nest. Specifically, the hyper-functioning noradrenergic locus coeruleus (LC) enables pups to learn rapid, robust preference for the caregiver. Conversely, a hypo-functional amygdala appears to prevent the infant from learning aversions to the caregiver. Adult LC and amygdala functional emergence correlates with sensitive period termination. This study suggests the neonatal brain is not an immature version of the adult brain but is uniquely designed to optimize attachment to the caregiver. Although human attachment may not rely on identical circuitry, the work reviewed here suggests a new conceptual framework in which to explore human attachments, particularly attachments to abusive caregivers.

Behavioral sciences (Basel, Switzerland), 2012

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, th...

Proceedings of the National Academy of Sciences of the United States of America, 2014

Emotional trauma is transmitted across generations. For example, children witnessing their parent expressing fear to specific sounds or images begin to express fear to those cues. Within normal range, this is adaptive, although pathological fear, such as occurs in posttraumatic stress disorder or specific phobias, is also socially transmitted to children and is thus of clinical concern. Here, using a rodent model, we report a mother-to-infant transfer of fear to a novel peppermint odor, which is dependent on the mother expressing fear to that smell in pups' presence. Examination of pups' neural activity using c-Fos early gene expression and 14 C 2-deoxyglucose autoradiography during mother-to-infant fear transmission revealed lateral and basal amygdala nuclei activity, with a causal role highlighted by pharmacological inactivation of pups' amygdala preventing the fear transmission. Maternal presence was not needed for fear transmission, because an elevation of pups' corticosterone induced by the odor of the frightened mother along with a novel peppermint odor was sufficient to produce pups' subsequent aversion to that odor. Disruption of axonal tracts from the Grueneberg ganglion, a structure implicated in alarm chemosignaling, or blockade of pups' alarm odor-induced corticosterone increase prevented transfer of fear. These memories are acquired at younger ages compared with amygdala-dependent odorshock conditioning and are more enduring following minimal conditioning. Our results provide clues to understanding transmission of specific fears across generations and its dependence upon maternal induction of pups' stress response paired with the cue to induce amygdala-dependent learning plasticity. Results are discussed within the context of caregiver emotional responses and adaptive vs. pathological fears social transmission. necklace glomeruli | pheromone | olfaction | PTSD | social referencing