Mesocorticolimbic Dopamine Pathways Across Adolescence: Diversity in Development

Mesocorticolimbic dopamine circuity undergoes a protracted maturation during adolescent life. Stable adult levels of behavioral functioning in reward, motivational, and cognitive domains are established as these pathways are refined, however, their extended developmental window also leaves them vulnerable to perturbation by environmental factors. In this review, we highlight recent advances in understanding the mechanisms underlying dopamine pathway development in the adolescent brain, and how the environment influences these processes to establish or disrupt neurocircuit diversity. We further integrate these recent studies into the larger historical framework of anatomical and neurochemical changes occurring during adolescence in the mesocorticolimbic dopamine system. While dopamine neuron heterogeneity is increasingly appreciated at molecular, physiological, and anatomical levels, we suggest that a developmental facet may play a key role in establishing vulnerability or resilience to environmental stimuli and experience in distinct dopamine circuits, shifting the balance between healthy brain development and susceptibility to psychiatric disease.

Multifinality, equifinality, and fanning: Developmental concepts and statistical implications

Multifinality, equifinality, and fanning are important developmental concepts that emphasize understanding interindividual variability in trajectories over time. However, each concept implies that there are points in a developmental window where interindividual variability is more limited. We illustrate the multifinality concept under manipulations of variance in starting points, using both normal and zero-inflated simulated data. Results indicate that standardized estimates and effect sizes are inflated when predicting components of growth models with limited interindividual variance, which could lead to overinterpretation of the practical importance of findings. Conceptual implications are considered and recommendations are provided for evaluating developmental changes in common situations that researchers may encounter.

Antagonistic activities of cotranscriptional regulators within an early developmental window set FLC expression level

Quantitative variation in expression of the Arabidopsis floral repressor FLC influences whether plants overwinter before flowering, or have a rapid cycling habit enabling multiple generations a year. Genetic analysis has identified activators and repressors of FLC expression but how they interact to set expression level is poorly understood. Here, we show that antagonistic functions of the FLC activator FRIGIDA (FRI) and the repressor FCA, at a specific stage of embryo development, determine FLC expression and flowering. FRI antagonizes an FCA-induced proximal polyadenylation to increase FLC expression and delay flowering. Sector analysis shows that FRI activity during the early heart stage of embryo development maximally delays flowering. Opposing functions of cotranscriptional regulators during an early embryonic developmental window thus set FLC expression levels and determine flowering time.

Negative play contagion in calves

Play is a strong outwardly directed, emotional behaviour and can contagiously spread between individuals. It has been suggested that high-playing animals could ‘seed’ play in others, spreading positive affective states. Despite the current interest in play contagion there has been no previous attempt to measure the strength of the play contagion effect. The calf (Bos taurus) is ideal for testing the strength of play contagion as play in calves is strongly related to energy intake from milk. We manipulated play in calves through their milk allowances and housed the calves in uniform groups all on the same milk allowance (high = UHigh or low = ULow) or in mixed groups with calves in the same group receiving either a high (= MHigh) or low (= MLow) milk allowance. We measured locomotor play using accelerometers on two consecutive days when calves were four and eight weeks old, in order to study play contagion over a protracted developmental window. We anticipated that differences in the level of play contagion between treatment groups would result in difference in the play levels observed in the MLow and ULow individuals. Contrary to our expectations we found that spontaneous play was suppressed in the high-milk calves housed in mixed groups (MHigh), in comparison to calves housed with group mates all receiving high-milk (UHigh). These results are the first to quantify a negative play contagion effect, particularly in a situation of long-term contact, and may suggest that negative contagion has a stronger effect on play behaviour than positive contagion.

Developmental asymmetries in learning to adjust to cooperative and uncooperative environments

Learning to successfully navigate social environments is a critical developmental goal, predictive of long-term wellbeing. However, little is known about how people learn to adjust to different social environments, and how this behaviour emerges across development. Here, we use a series of economic games to assess how children, adolescents, and young adults learn to adjust to social environments that differ in their level of cooperation (i.e., trust and coordination). Our results show an asymmetric developmental pattern: adjustment requiring uncooperative behaviour remains constant across adolescence, but adjustment requiring cooperative behaviour improves markedly across adolescence. Behavioural and computational analyses reveal that age-related differences in this social learning are shaped by age-related differences in the degree of inequality aversion and in the updating of beliefs about others. Our findings point to early adolescence as a phase of rapid change in cooperative behaviours, and highlight this as a key developmental window for interventions promoting well-adjusted social behaviour.

Cytoplasmic sharing through apical membrane remodeling

Multiple nuclei sharing a common cytoplasm are found in diverse tissues, organisms, and diseases. Yet, multinucleation remains a poorly understood biological property. Cytoplasm sharing invariably involves plasma membrane breaches. In contrast, we discovered cytoplasm sharing without membrane breaching in highly resorptive Drosophila rectal papillae. During a six-hour developmental window, 100 individual papillar cells assemble a multinucleate cytoplasm, allowing passage of proteins of at least 62 kDa throughout papillar tissue. Papillar cytoplasm sharing does not employ canonical mechanisms such as incomplete cytokinesis or muscle fusion pore regulators. Instead, sharing requires gap junction proteins (normally associated with transport of molecules < 1 kDa), which are positioned by membrane remodeling GTPases. Our work reveals a new role for apical membrane remodeling in converting a multicellular epithelium into a giant multinucleate cytoplasm.