Réponses de peur et développement : ontogenèse des vocalisations ultrasoniques et du décours temporel de la réponse dans un conditionnement de peur à l’odeur chez le rat

Fear allows individuals to react to an aversive stimulus by a defense response adapted to the situation. It can be triggered by naturally aversive stimuli or in response to stimuli that acquired an aversive valence through associative learning. This thesis investigated the characteristics and modifications of fear responses to these two types of stimuli throughout ontogeny. The studies presented here used olfactory fear conditioning in rat, in which an odor is paired with an aversive event and allows to rapidly induce long lasting odor fear memories. Defense responses can then be studied both to the learned odor and to the naturally aversive stimulus. We showed in particular that fear response to the learned odor presents a temporal pattern correlated with the duration of the time interval between the odor and the aversive event, showing that rats can learn about time and they do so at the youngest ages studied here, before the maturation of the brain structures classically involved in interval timing. We also studied the ultrasonic vocalizations emitted in response to the aversive stimulus and their changes throughout ontogeny. We described two types of vocalizations in pups that differ in their characteristics and emission context, suggesting they could have different functions, which needs further exploration. These thesis findings highlight that although the rat’s defense responses changes through ontogeny, the ability to produce temporally adapted responses occurs from the youngest ageLa peur est ce qui permet de réagir à un stimulus aversif par une réponse de défense adaptée à la situation. Elle peut être générée par un ensemble de stimuli naturellement aversifs ou par des stimuli ayant acquis une valeur aversive par apprentissage associatif. Cette thèse a pour but d'étudier les caractéristiques et modifications de la réponse de peur à ces deux types de stimuli au cours de l'ontogenèse. Les études présentées ici utilisent un conditionnement de peur à l'odeur chez le rat qui associe une odeur à un stimulus aversif et permet d'induire très rapidement et durablement des mémoires de peur à l'odeur. La réponse de défense peut alors être étudiée à la fois envers l'odeur apprise et envers le stimulus naturellement aversif. Nous montrons en particulier que la réponse de peur à l'odeur apprise présente un décours temporel corrélé à la durée de l'intervalle de temps entre l'odeur et le stimulus aversif, permettant d'affirmer que les animaux mémorisent et estiment le temps, et ce dès les premiers âges étudiés, avant la maturation des structures cérébrales classiquement impliquées dans cette mémoire temporelle. Par ailleurs, nous nous sommes intéressés aux vocalisations ultrasonores émises en réponse au stimulus aversif et à leur modification au cours de l'ontogenèse. Nous avons mis en évidence deux types de vocalisations chez le raton, dont les caractéristiques et critères d'induction laissent présager un rôle différentiel qui reste à explorer. L'ensemble de ces travaux soulignent que, même si les réponses de défense du rat changent au cours du développement, la capacité à produire ces réponses de manière temporellement adaptée est observée dès le plus jeune âg

Increasing Role of Maternal Immune Activation in Neurodevelopmental Disorders

The earliest stages of development are critically sensitive to environmental insults. An unfortunately timed stress on the developing brain can have dramatic consequences for the neurodevelopment and future mental health of the individual. In particular, infection of the mother during pregnancy has been correlated with increased risk of psychiatric and neurodevelopmental disorders. Evidence suggests that maternal immune activation, independently from the infection itself, can be responsible for the outcome in the offspring. This recognition has resulted in expanding study designs from epidemiologic correlations to the search for a causal relationship between activation of the maternal immune system and cognitive consequences for the offspring. However, this causality analysis remained limited in humans until recent work that longitudinally linked specific markers of maternal inflammation during pregnancy with alterations of the newborn brain and cognitive development of toddlers. This focused narrative review compares and discusses the results of these recent studies and places them into the broader landscape of maternal immune activation literature. New data point, in particular, to the association between the levels of interleukin 6 (IL-6) and modifications of the offspring’s salience network and subsequent cognitive impairments. This article further emphasizes the need to carefully control for potential confounders in studying the effects of maternal immune activation on the neonatal brain as well as the under-investigated consequences of intra-partum fever on offspring neurodevelopment

Updating temporal expectancy of an aversive event engages striatal plasticity under amygdala control

Pavlovian aversive conditioning requires learning of the association between a conditioned stimulus (CS) and an unconditioned, aversive stimulus (US) but also involves encoding the time interval between the two stimuli. The neurobiological bases of this time interval learning are unknown. Here, we show that in rats, the dorsal striatum and basal amygdala belong to a common functional network underlying temporal expectancy and learning of a CS–US interval. Importantly, changes in coherence between striatum and amygdala local field potentials (LFPs) were found to couple these structures during interval estimation within the lower range of the theta rhythm (3–6 Hz). Strikingly, we also show that a change to the CS–US time interval results in long-term changes in cortico-striatal synaptic efficacy under the control of the amygdala. Collectively, this study reveals physiological correlates of plasticity mechanisms of interval timing that take place in the striatum and are regulated by the amygdala

Updating temporal expectancy of an aversive event engages striatal plasticity under amygdala control

Pavlovian aversive conditioning requires learning of the association between a conditioned stimulus (CS) and an unconditioned, aversive stimulus (US) but also involves encoding the time interval between the two stimuli. The neurobiological bases of this time interval learning are unknown. Here, we show that in rats, the dorsal striatum and basal amygdala belong to a common functional network underlying temporal expectancy and learning of a CS–US interval. Importantly, changes in coherence between striatum and amygdala local field potentials (LFPs) were found to couple these structures during interval estimation within the lower range of the theta rhythm (3–6 Hz). Strikingly, we also show that a change to the CS–US time interval results in long-term changes in cortico-striatal synaptic efficacy under the control of the amygdala. Collectively, this study reveals physiological correlates of plasticity mechanisms of interval timing that take place in the striatum and are regulated by the amygdala

The Human Affectome

Over the last decades, the interdisciplinary field of the affective sciences has seen proliferation rather than integration of theoretical perspectives. This is due to differences in metaphysical and mechanistic assumptions about human affective phenomena (what they are and how they work) which, shaped by academic motivations and values, have determined the affective constructs and operationalizations. An assumption on the purpose of affective phenomena can be used as a teleological principle to guide the construction of a common set of metaphysical and mechanistic assumptions—a framework for human affective research. In this capstone paper for the special issue “Towards an Integrated Understanding of the Human Affectome”, we gather the tiered purpose of human affective phenomena to synthesize assumptions that account for human affective phenomena collectively. This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research

Fear responses and development : ontogeny of ultrasonic vocalizations and temporal pattern of the response in olfactory fear conditioning in rats

La peur est ce qui permet de réagir à un stimulus aversif par une réponse de défense adaptée à la situation. Elle peut être générée par un ensemble de stimuli naturellement aversifs ou par des stimuli ayant acquis une valeur aversive par apprentissage associatif. Cette thèse a pour but d'étudier les caractéristiques et modifications de la réponse de peur à ces deux types de stimuli au cours de l'ontogenèse. Les études présentées ici utilisent un conditionnement de peur à l'odeur chez le rat qui associe une odeur à un stimulus aversif et permet d'induire très rapidement et durablement des mémoires de peur à l'odeur. La réponse de défense peut alors être étudiée à la fois envers l'odeur apprise et envers le stimulus naturellement aversif. Nous montrons en particulier que la réponse de peur à l'odeur apprise présente un décours temporel corrélé à la durée de l'intervalle de temps entre l'odeur et le stimulus aversif, permettant d'affirmer que les animaux mémorisent et estiment le temps, et ce dès les premiers âges étudiés, avant la maturation des structures cérébrales classiquement impliquées dans cette mémoire temporelle. Par ailleurs, nous nous sommes intéressés aux vocalisations ultrasonores émises en réponse au stimulus aversif et à leur modification au cours de l'ontogenèse. Nous avons mis en évidence deux types de vocalisations chez le raton, dont les caractéristiques et critères d'induction laissent présager un rôle différentiel qui reste à explorer. L'ensemble de ces travaux soulignent que, même si les réponses de défense du rat changent au cours du développement, la capacité à produire ces réponses de manière temporellement adaptée est observée dès le plus jeune âgeFear allows individuals to react to an aversive stimulus by a defense response adapted to the situation. It can be triggered by naturally aversive stimuli or in response to stimuli that acquired an aversive valence through associative learning. This thesis investigated the characteristics and modifications of fear responses to these two types of stimuli throughout ontogeny. The studies presented here used olfactory fear conditioning in rat, in which an odor is paired with an aversive event and allows to rapidly induce long lasting odor fear memories. Defense responses can then be studied both to the learned odor and to the naturally aversive stimulus. We showed in particular that fear response to the learned odor presents a temporal pattern correlated with the duration of the time interval between the odor and the aversive event, showing that rats can learn about time and they do so at the youngest ages studied here, before the maturation of the brain structures classically involved in interval timing. We also studied the ultrasonic vocalizations emitted in response to the aversive stimulus and their changes throughout ontogeny. We described two types of vocalizations in pups that differ in their characteristics and emission context, suggesting they could have different functions, which needs further exploration. These thesis findings highlight that although the rat’s defense responses changes through ontogeny, the ability to produce temporally adapted responses occurs from the youngest ag

Ultrasonic Vocalizations Emission across Development in Rats: Coordination with Respiration and Impact on Brain Neural Dynamics

International audienceRats communicate using ultrasonic vocalizations (USV) throughout their life when confronted with emotionally stimulating situations, either negative or positive. The context of USV emission and the psychoacoustic characteristics of the vocalizations change greatly between infancy and adulthood. Importantly, the production of USV is tightly coordinated with respiration, and respiratory rhythm is known to influence brain activity and cognitive functions. This review goes through the acoustic characteristics and mechanisms of production of USV both in infant and adult rats and emphasizes the tight relationships that exist between USV emission and respiration throughout the rat’s development. It further describes how USV emission and respiration collectively affect brain oscillatory activities. We discuss the possible association of USV emission with emotional memory processes and point out several avenues of research on USV that are currently overlooked and could fill gaps in our knowledge