Integrated behavioral responses to emotionally salient stimuli require the concomitant activation of descending neural circuits that integrate physiological, affective, and motor responses to stress. Our previous work interrogated descending circuits in the brainstem and spinal cord that project to motor and sympathetic targets. The hypothalamic paraventricular nucleus (PVN), a key node of this circuitry, integrates multiple motor and sympathetic responses activated by stress. The present study sought to determine whether descending projections from the PVN to targets in muscle and adrenal gland are differentially organized in rats with inborn differences in emotionality and stress responsivity. We utilized retrograde transsynaptic tract‐tracing with unique pseudorabies virus (PRV) recombinants that were injected into sympathectomized gastrocnemius muscle and adrenal gland in two rat models featuring inborn differences in emotional behavior. Our tract‐tracing results revealed a significant decrease in the number of PVN neurons with poly‐synaptic projections to the gastrocnemius in male Wistar Kyoto [WKY] rats (versus Sprague Dawley rats) and selectively bred Low Novelty Responder [bLR] rats (versus selectively bred High Novelty Responder [bHR] rats). These neuroanatomical differences mirrored behavioral observations showing that both WKY and bLR rats display marked inhibition of emotional motor responses in a variety of settings relative to their respective controls. Our findings suggest that, in male rodents, PVN poly‐synaptic projections to skeletal muscle may regulate emotional motor and coping responses to stress. More broadly, perturbations in PVN motor circuitry may play a role in mediating psychomotor disturbances observed in depression or anxiety‐related disorders.
Evidence in humans and rodents suggests that perinatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants can have serious long‐term consequences in offspring exposed in utero or infancy via breast milk. In spite of this, there is limited knowledge of how perinatal SSRI exposure impacts brain development and adult behaviour. Children exposed to SSRIs in utero exhibit increased internalizing behaviour and abnormal social behaviour between the ages of 3 and 6, and increased risk of depression in adolescence; however, the neurobiological changes underlying this behaviour are poorly understood. In rodents, perinatal SSRI exposure perturbs hippocampal gene expression and alters adult emotional behaviour (including increased depression‐like behaviour). The present study demonstrates that perinatal exposure to the SSRI paroxetine leads to DNA hypomethylation and reduces DNA methyltransferase 3a (Dnmt3a) mRNA expression in the hippocampus during the second and third weeks of life. Next‐generation sequencing identified numerous differentially methylated genomic regions, including altered methylation and transcription of several dendritogenesis‐related genes. We then tested the hypothesis that transiently decreasing Dnmt3a expression in the early postnatal hippocampus would mimic the behavioural effects of perinatal SSRI exposure. We found that siRNA‐mediated knockdown of Dnmt3a in the dentate gyrus during the second to third week of life produced greater depression‐like behaviour in adult female (but not male) offspring, akin to the behavioural consequences of perinatal SSRI exposure. Overall, these data suggest that perinatal SSRI exposure may increase depression‐like behaviours, at least in part, through reduced Dnmt3a expression in the developing hippocampus.
Stressful experiences during childhood, including poverty and inconsistent parental care, can enhance vulnerability for worsened physical and mental health outcomes in adulthood. Using Sprague Dawley rats, the present study explored the impact of limited resource availability on maternal behavior and physiological and emotional behavior outcomes in the offspring. Early life adversity was induced by incorporating aspects of the limited bedding and nesting and scarcity models, wherein limited resource availability has previously been shown to provoke unpredictable or adverse maternal care respectively. In our hands, neonatal limited bedding (NLB) stress during postnatal days (P)2–9 altered maternal care, augmenting pup‐directed behaviors and reducing self‐directed behaviors, and modestly increased the frequency of transitions between discrete behaviors across consecutive timed observations. NLB‐exposed pups had lower core body temperatures immediately following the stressful manipulation and exhibited decreased body weight gain across development. However, NLB exposure did not impact adult offspring's social or emotional behavior outcomes in the three‐chamber social interaction, novelty‐suppressed feeding, splash, or forced swim tests. These findings add to the literature demonstrating that early life adversity impacts maternal care in rodents and can disrupt certain metabolic and thermoregulatory outcomes in the offspring.
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