Children and adolescents face a wide variety of developmental changes and environmental challenges, and it is estimated that at least one in five children aged 3–17 will experience behavioral or mental health issues. This period of life coincides with major changes in brain structure and function that have profound long-term consequences for learning, decision-making (including risk taking), and emotional processing. For example, continued development of the prefrontal cortex in adolescence is a sensitive period during which individuals are particularly susceptible to risky behaviors, environmental stressors, and substance use. While recent advances in mental health literacy programs have paved the way for increased awareness of the benefits of mental health curricula in schools, these efforts could be greatly bolstered with support in basic neuroscience education in developmentally appropriate and area-specific content. Here, we provide a discussion on the basic structural and functional changes occurring in the brain throughout childhood, how this contributes to changes in cognitive function, and the risk factors posed by early life adversity, stress, and drug use. Finally, we provide a perspective on the benefits of integrating findings from the field of neuroscience and suggestions for tools to better equip students, teachers, administrators, and school mental health staff to provide new directions for addressing the mental health crises faced by millions of children and youth each year.

Adaptive decision-making requires the ability to weigh the relative costs versus the benefits of our actions and to flexibly respond to changing environmental contingencies. While midbrain dopamine (DA) has been a major focus of study for its role in associative learning, motivation, and reward seeking, far less is known regarding the contribution of inhibitory dopamine inputs in promoting behavioral inhibition and avoidance learning. The rostromedial tegmental nucleus (RMTg) sends dense GABAergic projections to DA neurons in the ventral tegmental area (VTA) and mounting evidence suggests the RMTg-VTA circuit is required to suppress reward seeking under punishment, but it remains unclear whether stimulation of this pathway is sufficient to drive learning and promote shifts in cost-benefit decisions. To test this, we developed two separate tasks of passive and active avoidance in rats where lever pressing for food reward was associated with repeated stimulation of the RMTg-VTA circuit. In a one-lever fixed ratio 5 food-seeking task, we found that pairing contingent RMTg-VTA stimulation immediately after responding for reward delivery caused a robust, yet transient suppression of reward seeking that quickly returned to baseline after stimulation ceased. When given an alternative reward choice, however, RMTg-VTA stimulation caused a rapid and enduring shift in subjective choice leading to persistent and selective avoidance of the stimulation-paired reward. These findings support a multifaceted role for the RMTg-VTA pathway in learning and decision-making and provide key insights into the neural mechanisms underlying behavioral avoidance and cost-benefit decisions.

Aging is associated with decline in spatial learning, cognitive flexibility, and working memory, yet the extent to which biological sex modulates changes in cognitive function remains unresolved. While sex differences are evident in pathological brain aging, sparse insights from healthy aging populations suggest that sex effects on cognition are modest and domain specific. To systematically test effects of biological sex across the life span on specific aspects of cognitive function, we examined age- and sex-related changes in spatial cognition in a large cohort of Fischer 344 rats (N = 373), including young (4–8 months), middle-aged (12–16 months), and older aged (22–26 months) males and females. Rats were assessed on spatial reference learning, reversal learning, and working memory versions of the Morris water maze, with performance quantified using proximity-based measures, providing sensitive, individualized indices of spatial learning. Across all tasks, age accounted for the largest proportion of variance, with older rats exhibiting impairments in spatial learning, flexibility, and working memory relative to young adults. In contrast, effects of sex or interactions with age were limited to certain aspects of performance and were substantially smaller relative to age and training effects. Specifically, a female-specific association between spatial reference memory and reversal learning was observed despite comparable overall performance. Performance on visible platform control trials did not indicate gross sensorimotor impairments that would account for age-related spatial deficits. Together, findings demonstrate age is the primary determinant of spatial cognitive decline under normative conditions, while sex-related influences, if present, are subtle and task-dependent.

Addiction is marked by aberrant decision-making and an inability to suppress inappropriate and often dangerous behaviors. We previously demonstrated that inactivation of the rostromedial tegmental nucleus (RMTg) in rats causes persistent food seeking despite impending aversive footshock, an effect strikingly similar to the punishment resistance observed in people with a history of protracted drug use [1]. Here, we extend these studies to demonstrate chemogenetic silencing of RMTg axonal projections to the ventral tegmental area (VTA) (RMTg◊VTA pathway) causes rats to endure significantly more footshock to receive cocaine infusions. To further test whether activation of this circuit is sufficient to suppress reward seeking in the absence of an overtly aversive stimulus, we used temporally specific optogenetic stimulation of the RMTg◊VTA pathway as a “punisher” in place of footshock following lever pressing for either food or cocaine reward. While optical stimulation of the RMTg◊VTA pathway robustly suppressed lever pressing for food, we found that stimulation of this circuit had only modest effects on suppressing responding for cocaine infusions. Even though optical RMTg◊VTA stimulation was not particularly effective at reducing ongoing cocaine use, this experience nevertheless had long-lasting consequences, as reinstatement of drug seeking in response to cocaine-associated cues was profoundly suppressed when tested nearly two weeks later. These results suggest the RMTg may serve as a useful target for producing enduring reductions in drug craving, particularly during periods of abstinence from drug use.

Adaptive decision-making requires the ability to weigh the relative costs versus the benefits of our actions and to flexibly respond to changing environmental contingencies. While midbrain dopamine (DA) has been a major focus of study for its role in associative learning, motivation, and reward seeking, far less is known regarding the contribution of inhibitory dopamine inputs in promoting behavioral inhibition and avoidance learning. The rostromedial tegmental nucleus (RMTg) sends dense GABAergic projections to DA neurons in the ventral tegmental area (VTA) and mounting evidence suggests the RMTg–VTA circuit is required to suppress reward seeking under punishment, but it remains unclear whether stimulation of this pathway is sufficient to drive learning and promote shifts in cost-benefit decisions. To test this, we developed two separate tasks of passive and active avoidance in rats where lever pressing for food reward was associated with repeated contingent optogenetic stimulation of the RMTg–VTA pathway. In a one-lever fixed ratio 5 food-seeking task, we found that pairing RMTg–VTA stimulation with reward delivery caused a robust, yet transient suppression of reward seeking that quickly returned to baseline after contingent stimulation ceased. When given an alternative reward choice, however, RMTg–VTA stimulation caused a rapid and enduring shift in subjective choice leading to persistent and selective avoidance of the stimulation-paired reward. These findings support a multifaceted role for the RMTg–VTA pathway in learning and decision-making and provide key insights into the neural mechanisms underlying behavioral avoidance and maladaptive reward seeking.