Biology subjects

Demaestri, C.

Publications and source records attributed to Demaestri, C..

4 recordsLinked to original sources

bioRxiv2025

Behavioral Opportunism and Altered Dopamine Dynamics in Mice Exposed to Early Life Adversity

Early life adversity (ELA) confers risk for reward-related psychopathologies. These risks may stem from adaptations optimizing reward pursuit in anticipation of unreliable, resource poor environments. One rational adaptation to poor, unreliable environments is Behavioral Opportunism: updating expectations more slowly and acting vigorously only when reward is immediately available. To systematically test the impact of ELA on behavioral strategies and underlying reward processing mechanisms, we exposed mice to resource restriction (limited bedding and nesting materials for 7 days) to manipulate the reliability and quality of early life care. Subsequently, we tested adults reward learning and decision making in a two-arm bandit task and recorded dopamine signaling using dLight1.2 fiber photometry in the nucleus accumbens core. Exposure to ELA led to poorer choice discrimination, impaired learning, and decreased adaptation to changes in reward availability. Furthermore, ELA mice were slower to choose between levers but were faster to retrieve immediately available rewards when delivered, consistent with a strategy of behavioral opportunism. Dopamine signaling predicted behavior in both rearing conditions, and its fluctuations were strongly predictive of faster retrieval in ELA mice and an increased likelihood of choice repetition, implying that aberrant dopamine signals underlie slowed learning and vigorous action for immediately available rewards. To understand key features of maternal interactions driving these effects, we used home cage video monitoring to quantify maternal behaviors, continuously, across early life. We found that specific experiential outcomes, such as maternal kicking, intensified behavioral opportunism in adults, predicting poorer bandit task performance beyond the group effect of ELA. Behavioral opportunism provides an explanatory framework for interpreting altered reward processing and reward pursuit in adulthood for individuals exposed to ELA.

animal behavior and cognition↗

bioRxiv2023

Early life adversity reduces affiliative behavior towards a distressed cagemate and leads to sex-specific alterations in corticosterone responses

Experiencing early life adversity (ELA) alters stress physiology and increases the risk for developing psychiatric disorders. The social environment can influence dynamics of stress responding and buffer and/or transfer stress across individuals. Yet, the impact of ELA on sensitivity to the stress of others and social behavior following stress is unknown. Here, to test the impact of ELA on social and physiological responses to stress, circulating blood corticosterone (CORT) and social behaviors were assessed in adult male and female mice reared under limited bedding and nesting (LBN) or control conditions. To induce stress, one cagemate of a pair-housed cage underwent a footshock paradigm and was then returned to their unshocked partner. CORT was measured in both mice 20 or 90 minutes after stress exposure, and social behaviors were recorded and analyzed. ELA rearing influenced the CORT response to stress in a sex-specific manner. In males, both control and ELA-reared mice exhibited similar stress transfer to unshocked cagemates and similar CORT dynamics. In contrast, ELA females showed a heightened stress transfer to unshocked cagemates, and sustained elevation of CORT relative to controls, indicating enhanced stress contagion and a failure to terminate the stress response. Behaviorally, ELA females displayed decreased allogrooming and increased investigative behaviors, while ELA males showed reduced huddling. Together, these findings demonstrate that ELA influenced HPA axis dynamics, social stress contagion and social behavior. Further research is needed to unravel the underlying mechanisms and long-term consequences of ELA on stress systems and their impact on behavioral outcomes.

neuroscience↗

bioRxiv2019

Too much, too young? Altered corticolimbic axonal innervation and resting state functional connectivity suggests sex-dependent outcomes in a rat model of early life adversity

Adverse early experiences significantly alter behavioral and neural trajectories via aberrant brain maturation. Children with a history of early life stress (ELS) exhibit maladaptive behaviors and increased risk of mental illness later in life. Evidence in ELS-exposed humans identifies a role of atypical corticolimbic development; specifically, within amygdala-prefrontal cortex (PFC) circuits, and show precocially mature task-based corticolimbic functional connectivity (FC). However, the neurobiological substrates of such ELS-driven developmental changes remain unknown. Here, we identify putative neurobiological changes to determine the timeline of developmental perturbations following ELS in rats. Anterograde axonal tracing from basolateral amygdala (BLA) to pre- and infralimbic (PL, IL) PFC was quantified at postnatal days (PD)28, 38, and 48, along with anxiety-like behavior, in maternally separated (ELS) or control reared (CON) male and female rats. Resting state (rs)FC was assessed at PD28 and PD48 in a separate cohort. We report that ELS-exposed female rats show early maturation of BLA-PFC innervation at PD28, with ELS-related changes in males not appearing until PD38. ELS disrupted the maturation of rsFC from PD28 to PD48 in females, with enduring relationships between early rsFC and later anxiety-like behavior. Only transient ELS-related changes in rsFC were seen in male PL. Together, these data provide evidence that female rats may be more vulnerable to the effects of ELS via precocial BLA-PFC innervation, which may drive altered corticolimbic rsFC. These data also provide evidence that increased BLA-IL rsFC is associated with behavioral resiliency following ELS in female rats, providing mechanistic insight into the underlying etiology of adversity-induced vulnerability and resiliency.

neuroscience↗

bioRxiv2018

22kHz and 55kHz ultrasonic vocalizations differentially influence neural and behavioral outcomes: Implications for modeling anxiety via auditory stimuli in the rat

The communicative role of ultrasonic vocalizations (USVs) in rodents is well established, with distinct USVs indicative of different affective states. USVs in the 22kHz range are typically emitted by adult rats when in anxiety-or fear-provoking situations (e.g. predator odor, social defeat), while 55kHz range USVs are emitted in appetitive situations (e.g., play, anticipation of reward). Previous work indicates that USVs (real-time and playback) can effectively communicate these affective states and influence changes in behavior and neural activity of the receiver. Changes in cFos activation following 22kHz USVs have been seen in cortical and limbic regions involved in anxiety, including the basolateral amygdala (BLA). However, it is unknown how USV playback influences cFos activity within the basal nucleus of the stria terminalis (BNST), a region also thought to be critical in processing anxiety-related information. The present work sought to characterize distinct behavioral, physiological, and neural responses in rats presented with aversive (22kHz) compared to appetitive (55kHz) USVs or silence. Our findings show that rats exposed to 22kHz USVs: 1) engage in anxiety-like behaviors in the open field and elevated zero maze, and 2) show distinct patterns of cFos activation within the BLA and BNST that contrast those seen in 55kHz playback. Specifically, 22kHz USVs increased cFos density in the anterodorsal nuclei, while 55kHz playback increased cFos in the oval nucleus of the BNST. These results provide important groundwork for leveraging ethologically-relevant stimuli in the rat to improve our understanding of anxiety-related responses in both typical and pathological populations.

neuroscience↗