Biology subjects

Wilbrecht, L.

Publications and source records attributed to Wilbrecht, L..

At least 19 recordsLinked to original sources

bioRxiv2026

Genomic signatures of selection in the mound-building mouse Mus spicilegus

The steppe mouse Mus spicilegus is distinguished by several unusual phenotypes: animals of this species build complex mounds from brush and dirt, and this behavior as well as the pace of development is regulated by season of birth. The genetic and evolutionary basis of species-defining traits in Mus spicilegus is unknown. To discover genomic clues to the mechanisms at play, we took a molecular-evolution approach. Sequence-based tests of protein-coding exons, and of brain-active cis-regulatory regions, revealed a striking excess of evidence for evolutionary acceleration in the M. spicilegus genome relative to those of closely related species. Transcriptional analyses also revealed unique expression programs in the M. spicilegus brain, which could be traced in part to cis-regulatory sequence variation. Hit loci from our molecular-evolution tests tended to be active in the cerebral cortices and hypothalamus and have annotated functions in neuronal development, neural plasticity, or endocrine signaling. In many cases, their orthologs in other animal systems had been implicated in neoteny/the pace of maturation, unusual building behaviors, and autism. Together, our data indicate that M. spicilegus has undergone divergence in brain-active genes to an extent far more than its relatives. We interpret the affected genes under a model in which they mediate the seasonal capacity by M. spicilegus for protracted maturation and mound-building. Thus our work provides an evolutionary interpretation of, and catalog of candidate determinants for, shifts in motivated behavior and development in this intriguing mouse species.

evolutionary biology↗

bioRxiv2025

Absence of testes at puberty impacts functional development of nigrostriatal but not mesoaccumbal dopamine terminals in a wild-derived mouse

The nigrostriatal and mesoaccumbal dopamine systems are thought to contribute to changes in behavior and learning during adolescence, yet it is unclear how the rise in gonadal hormones at puberty impacts the function of these systems. We studied the impact of prepubertal gonadectomy on evoked dopamine release in male Mus spicilegus, a mouse whose adolescent life history has been carefully characterized in the wild and laboratory. To examine how puberty impacts the dopamine systems in M. spicilegus males, we removed the gonads prepubertally at P25 and then examined evoked dopamine release in the dorsomedial, dorsolateral, and nucleus accumbens core regions of striatal slices at P60-70. To measure dopamine release, we used near-infrared catecholamine nanosensors (nIRCats) to enable study of spatial distribution of dopamine release sites in each striatal region. We found that prepubertal gonadectomy led to a significantly reduced density of dopamine release sites and reduced dopamine release at each site in the dorsolateral nigrostriatal system compared to sham controls. By contrast, mesoaccumbal dopamine release was comparable between sham and gonadectomized groups. Our data suggest that during adolescence the development of the nigrostriatal dopamine system is significantly affected by the rise in gonadal hormones in males, while the mesoaccumbal system shows no detectable sensitivity at this time point. These data are consistent with molecular studies in rodents that suggest nigrostriatal neurons are sensitive to androgens at puberty, and extend our understanding of how gonadal hormones could impact the spatial distribution and release potential of dopamine terminals in the striatum. Significance StatementHere we use a wild-derived species, Mus spicilegus, to study adolescent development. This wild-derived species has value over standard lab mice because it is more likely to exhibit evolved developmental programs relevant to dispersal and other natural behaviors. By using this wild-derived species and metrics of evoked dopamine release with spatial resolution, we can test if the rise in gonadal hormones at puberty plays a role in maturation of dopamine terminal function in the striatum. These findings may help us better understand developmental programs in humans that orchestrate changes in behavior at adolescent milestones in contexts of both health and disease.

neuroscience↗

bioRxiv2025

Genetic changes linked to two different syndromic forms of autism enhance reinforcement learning in adolescent male but not female mice

Autism Spectrum Disorder (ASD) is characterized by restricted and repetitive behaviors and social differences, both of which may manifest, in part, from underlying differences in corticostriatal circuits and reinforcement learning. Here, we investigated reinforcement learning in developing mice with mutations in either Tsc2 or Shank3, both high-confidence ASD risk genes associated with major syndromic forms of ASD. Using an odor-based two-alternative forced choice (2AFC) task, we tested early adolescent mice of both sexes and found male Tsc2 and Shank3B heterozygote (Het) mice showed enhanced learning performance compared to their wild type (WT) siblings. No gain of function was observed in females. Using a novel reinforcement learning (RL) based computational model to infer learning rate as well as policy-level task engagement and disengagement, we found that the gain of function in males was driven by an enhanced positive learning rate in both Tsc2 and Shank3B Het mice. The gain of function in Het males was absent when mice were trained with a probabilistic reward schedule. These findings in two ASD mouse models reveal a convergent learning phenotype that shows similar sensitivity to sex and environmental uncertainty. These data can inform our understanding of both strengths and challenges associated with autism, while providing further evidence that sex and experience of uncertainty modulate autism-related phenotypes. Significance StatementReinforcement learning is a foundational form of learning that is widely used in behavioral interventions for autism. Here, we measured reinforcement learning in developing mice carrying genetic mutations linked to two different syndromic forms of autism. We found that males showed strengths in reinforcement learning compared to their wild type siblings, while females showed no differences. This gain of function in males was no longer observed when uncertainty was introduced into the reward schedule for correct choices. These findings support a model in which diverse genetic changes interact with sex to generate common phenotypes underlying autism. Our data further support the idea that autism risk genes may produce strengths as well as challenges in behavioral function.

neuroscience↗

bioRxiv2024

The adolescent frontal cortex shows stronger population-level encoding of information than the adult during a putative sensitive period

Adolescence is commonly claimed to be a sensitive period for brain development, but it is not clear how experience at this stage can have such strong impacts. We hypothesized that enhanced sensitivity to experience during adolescence may manifest as stronger encoding of task-related information in the dorsomedial prefrontal cortex (dmPFC). To enable optical access to task-related layer 2/3 neural activity in the developing mouse dmPFC, we imaged mice under a 2-photon microscope while they learned an auditory go/no-go task. We found adolescent mice (postnatal day P30-45) learned the task to criterion faster than adult mice (P60-75). When we compared neural activity in expert mice with comparable performance between the two age groups, we found that a similar fraction of single cells encoded task variables in the two groups. However, task information could be better decoded from the adolescent dmPFC population activity than the adult, even when we controlled for differences in head-fixed running. Adolescents also showed greater noise correlation than adults and shuffling to remove this noise correlation suggested noise correlation contributed to gain of function in adolescent compared to adult brain. We suggest a working model for adolescent brain function in which greater noise correlation supports greater capacity for distributed encoding of information driving, for better or for worse, increased sensitivity to experiences at this stage of life.

neuroscience↗

bioRxiv2024

Optical Fibers Functionalized with Single-Walled Carbon Nanotubes for Flexible Fluorescent Catecholamine Detection

Despite the blockbuster popularity of drugs that act on catecholamine receptors, catecholamine dynamics in human health and disease remain an incomplete picture. Recent advances in fluorescent sensors have enabled unprecedented access to catecholamine dynamics in preclinical animal models, but the requirements of these technologies limit translational value for clinical diagnostics. Here, we present a flexible and convenient tool for fluorescent catecholamine detection by functionalizing optical fibers with single-walled carbon nanotube (SWNT)-based near-infrared catecholamine sensors (nIRCats), a form factor that has potential for more convenient and less invasive clinical translation. We show that these near-infrared functionalized (nIRF) fibers respond to dopamine in a biologically-relevant concentration range (10nM through 1 M) with a mean {Delta}F/F0 of 0.022 through 0.411, with no statistically significant effect on signal magnitude after 16-hour exposure to human blood plasma. We further demonstrate the utility of these fibers in as little as 10 L volumes of clinically relevant biofluids up to 24 weeks after preparation, with a {Delta}F/F0 of up to 0.059 through 1.127 for 10 nM through 1 M dopamine. We also introduce a compact, mobile dual-near-infrared fiber photometry rig and demonstrate its success detecting dopamine with 0.005 {Delta}F/F0 in acute brain slices with nIRF fibers. Together, this fiber-based tool and photometry rig expand the toolbox of catecholamine detection technologies to a broader range of applications.

biochemistry↗

bioRxiv2024

Hidden state inference requires abstract contextual representations in ventral hippocampus

The ability to form and utilize subjective, latent contextual representations to influence decision making is a crucial determinant of everyday life. The hippocampus is widely hypothesized to bind together otherwise abstract combinations of stimuli to represent such latent contexts, and to allow their use to support the process of hidden state inference. Yet, direct evidence for this remains limited. Here we show that the CA1 area of the ventral hippocampus is necessary for mice to perform hidden state inference during a 2-armed bandit task. vCA1 neurons robustly differentiate between the two abstract contexts required for this strategy in a manner similar to the differentiation of spatial locations, despite the contexts being formed only from past probabilistic outcomes. These findings offer insight into how latent contextual information is used to optimize decision-making processes, and emphasize a key role of the hippocampus in hidden state inference.

neuroscience↗

bioRxiv2024

Adolescent and adult mice use both incremental reinforcement learning and short term memory when learning concurrent stimulus-action associations

Computational modeling has revealed that human research participants use both rapid working memory (WM) and incremental reinforcement learning (RL) (RL+WM) to solve a simple instrumental learning task, relying on WM when the number of stimuli is small and supplementing with RL when the number of stimuli exceeds WM capacity. Inspired by this work, we examined which learning systems and strategies are used by adolescent and adult mice when they first acquire a conditional associative learning task. In a version of the human RL+WM task translated for rodents, mice were required to associate odor stimuli (from a set of 2 or 4 odors) with a left or right port to receive reward. Using logistic regression and computational models to analyze the first 200 trials per odor, we determined that mice used both incremental RL and stimulus-insensitive, one-back strategies to solve the task. While these one-back strategies may be a simple form of short-term or working memory, they did not approximate the boost to learning performance that has been observed in human participants using WM in a comparable task. Adolescent and adult mice also showed comparable performance, with no change in learning rate or softmax beta parameters with adolescent development and task experience. However, reliance on a one-back perseverative, win-stay strategy increased with development in males in both odor set sizes. Our findings advance a simple conditional associative learning task and new models to enable the isolation and quantification of reinforcement learning alongside other strategies mice use while learning to associate stimuli with rewards within a single behavioral session. These data and methods can inform and aid comparative study of reinforcement learning across species. Author summaryHere we studied the strategies and mechanisms mice use to learn a simple two choice odor based task in a single session. Using a set size manipulation and computational models we find evidence that mice use incremental reinforcement learning as well as several short-term (one-back) strategies to earn water reward. Our data and models clarify how mice learn a simple task and establish methods by which mouse and human reinforcement learning may be isolated for cross-species comparison of learning.

neuroscience↗

bioRxiv2023

Nucleus accumbens dopamine release reflects Bayesian inference during instrumental learning

Dopamine release in the nucleus accumbens has been hypothesized to signal reward prediction error, the difference between observed and predicted reward, suggesting a biological implementation for reinforcement learning. Rigorous tests of this hypothesis require assumptions about how the brain maps sensory signals to reward predictions, yet this mapping is still poorly understood. In particular, the mapping is non-trivial when sensory signals provide ambiguous information about the hidden state of the environment. Previous work using classical conditioning tasks has suggested that reward predictions are generated conditional on probabilistic beliefs about the hidden state, such that dopamine implicitly reflects these beliefs. Here we test this hypothesis in the context of an instrumental task (a two-armed bandit), where the hidden state switches repeatedly. We measured choice behavior and recorded dLight signals reflecting dopamine release in the nucleus accumbens core. Model comparison among a wide set of cognitive models based on the behavioral data favored models that used Bayesian updating of probabilistic beliefs. These same models also quantitatively matched the dopamine measurements better than non-Bayesian alternatives. We conclude that probabilistic belief computation contributes to instrumental task performance in mice and is reflected in mesolimbic dopamine signaling.

animal behavior and cognition↗

bioRxiv2021

Sex Differences in Pubertal Circadian and Ultradian Rhythmic Development Under Naturalistic Conditions

Biological rhythms in core body temperature (CBT) provide informative markers of adolescent development under controlled laboratory conditions. However, it is unknown if these markers are preserved under more variable naturalistic conditions, and if CBT may therefore prove useful in a real-world setting. To evaluate this possibility, we examined fecal steroid concentrations and CBT rhythms from pre-adolescence (p26) through early adulthood (p76) in intact male and female rats under natural light and climate at the University of California, Berkeley Field Station. Despite greater environmental variability, CBT markers of pubertal onset and its rhythmic progression were comparable to those previously reported in laboratory conditions in female rats and extend actigraphy-based findings in males. Specifically, sex differences emerged in circadian rhythm (CR) power and temperature amplitude prior to pubertal onset and persisted into early adulthood, with females exhibiting elevated CBT and decreased CR power compared to males. Within-day (ultradian rhythm; UR) patterns also exhibited a pronounced sex difference associated with estrous cyclicity. Pubertal onset, defined by vaginal opening, preputial separation, and sex steroid concentrations, occurred later than previously reported under lab conditions for both sexes. Vaginal opening and increased fecal estradiol concentrations were closely tied to the commencement of 4-day oscillations in CBT and UR power in female rats. By contrast, preputial separation and the first rise in testosterone concentration were not associated with adolescent changes to CBT rhythms in male rats. Together, males and females exhibited unique temporal patterning of CBT and sex steroids across pubertal development, with tractable associations between hormonal concentrations, external development, and temporal structure in females. The preservation of these features outside the laboratory supports CBT as a strong candidate for translational pubertal monitoring under naturalistic conditions in females.

physiology↗

bioRxiv2021

Adolescent Development of Biological Rhythms: Estradiol Dependence and Effects of Combined Contraceptives

PurposeAdolescence is a period of continuous development, including the maturation of endogenous rhythms across systems and timescales. Although these dynamic changes are well recognized, their continuous structure and hormonal dependence have not been systematically characterized. Given the well-established link between core body temperature (CBT) and reproductive hormones in adults, we hypothesized that high-resolution CBT can be applied to passively monitor pubertal development and disruption with high fidelity. MethodsTo examine this possibility, we used signal processing to investigate the trajectory of CBT rhythms at the within-day (ultradian), daily (circadian), and ovulatory timescales, their dependence on estradiol, and the effects of hormonal contraceptives. ResultsPuberty onset was marked by a rise in fecal estradiol (fE2), followed by an elevation in CBT and circadian power. This time period marked the commencement of 4-day rhythmicity in fE2, CBT, and ultradian power marking the onset of the estrous cycle. The rise in circadian amplitude was accelerated by E2 treatment, indicating a role for this hormone in rhythmic development. Contraceptive administration in later adolescence reduced CBT and circadian power and resulted in disruption to 4-day cycles that persisted after discontinuation. ConclusionsOur data reveal with precise temporal resolution how biological rhythms change across adolescence and demonstrate a role for E2 in the emergence and preservation of multiscale rhythmicity. These findings also demonstrate how hormones delivered exogenously in a non-rhythmic pattern can disrupt rhythmic development. These data lay the groundwork for a future in which temperature metrics provide an inexpensive, convenient method for monitoring pubertal maturation and support the development of hormone therapies that better mimic and support human chronobiology.

physiology↗

bioRxiv2021

Prepubertal ovariectomy alters dorsomedial striatum indirect pathway neuron excitability and explore/exploit balance in female mice

Decision-making circuits are modulated across life stages (e.g. juvenile, adolescent, or adult)--as well as on the shorter timescale of reproductive cycles in females--to meet changing environmental and physiological demands. Ovarian hormone signaling may contribute to this flexibility by regulating neural circuits involved in adaptive decision making. Here, we examined how prepubertal ovariectomy (pOVX) influences adult performance in an odor-guided multiple-choice reversal task. During reversal learning, pOVX females exhibited a distinct pattern of errors compared to sham-operated controls. To characterize decision strategies, we fit a reinforcement learning model to trial-by-trial behavior across both the initial Discrimination and Reversal phases. Sham females showed a significant increase in the inverse temperature parameter ({beta}) during Reversal, consistent with a shift towards a more exploitative choice policy favoring high-value options. By contrast, pOVX females failed to show a phase-dependent increase in {beta}, suggesting they continued to use a more exploratory strategy. To identify a neural correlate of this behavioral phenotype, we performed whole-cell patch clamp recordings within the dorsomedial striatum (DMS), a region implicated in regulating action selection and explore/exploit choice policy. Intrinsic excitability of dopamine receptor type 2-expressing (D2R) indirect pathway spiny projection neurons (iSPNs) was significantly higher in pOVX females compared to both sham-operated and unmanipulated controls. Finally, to test whether increased D2R(+) iSPN excitability could causally contribute to the exploratory reversal phenotype, we chemogenetically activated DMS D2R(+) neurons in intact female mice. This manipulation increased exploratory choice during reversal learning, recapitulating the pattern observed following pOVX. Together, these data suggest that pubertal status may influence how females adapt their decision strategy between Discrimination and Reversal phases, potentially through long-lasting modulation of DMS iSPN intrinsic excitability.

neuroscience↗

bioRxiv2021

Learning Rates Are Not All the Same: The Interpretation of Computational Model Parameters Depends on the Context

Reinforcement Learning (RL) models have revolutionized the cognitive and brain sciences, promising to explain behavior from simple conditioning to complex problem solving, to shed light on developmental and individual differences, and to anchor cognitive processes in specific brain mechanisms. However, the RL literature increasingly reveals contradictory results, which might cast doubt on these claims. We hypothesized that many contradictions arise from two commonly-held assumptions about computational model parameters that are actually often invalid: That parameters generalize between contexts (e.g., tasks, models) and that they capture interpretable (i.e., unique, distinctive) neurocognitive processes. To test this, we asked 291 participants aged 8-30 years to complete three learning tasks in one experimental session, and fitted RL models to each. We found that some parameters (exploration / decision noise) showed significant generalization: they followed similar developmental trajectories, and were reciprocally predictive between tasks. However, generalization was significantly below ceiling. Furthermore, other parameters (learning rates, forgetting) did not show evidence of generalization, and sometimes even opposite developmental trajectories. Interpretability was low for all parameters. We conclude that the systematic study of context factors (e.g., reward stochasticity; task volatility) will be necessary to enhance the generalizability and interpretability of computational cognitive models. HighlightsO_LIComputational cognitive modeling often makes two implicit assumptions: 1) Model parameters generalize between studies and models. 2) Parameters are interpretable, i.e., neurally, cognitively, and/or mechanistically specific. C_LIO_LIWe empirically investigate these assumptions in Reinforcement Learning (RL), using a large developmental dataset featuring three different learning tasks in a within-participant design. C_LIO_LIWe find that no parameters generalize between tasks in terms of absolute parameter values. However, RL decision noise/exploration parameters generalize in terms of between-participant variation, showing similar age trajectories across tasks. Interpretability was low for all parameters, especially those related to learning and memory. C_LIO_LIEven for parameters that showed generalization, the degree of generalization was significantly lower than in an artificial sample with perfect generalization for most parameters, revealing a relative lack of generalization. C_LIO_LIThese findings are in accordance with previous claims about the developmental trajectory of decision noise/exploration parameters, but suggest that claims about the development of learning rates or Forgetting might not be generalizable: these parameters are unlikely to capture the same neuro-cognitive processes across different tasks. C_LIO_LIWe suggest ways forward to improve the generalizability and interpretability of model parameters, in particular by focusing more on task context. C_LI

neuroscience↗

bioRxiv2020

Modeling Changes in Probabilistic Reinforcement Learning during Adolescence

In the real world, many relationships between events are uncertain and probabilistic. Uncertainty is also likely to be a more common feature of daily experience for youth because they have less experience to draw from than adults. Some studies suggests probabilistic learning may be inefficient in youth compared to adults [1], while others suggest it may be more efficient in youth that are in mid adolescence [2, 3]. Here we used a probabilistic reinforcement learning task to test how youth age 8-17 (N = 187) and adults age 18-30 (N = 110) learn about stable probabilistic contingencies. Performance increased with age through early-twenties, then stabilized. Using hierarchical Bayesian methods to fit computational reinforcement learning models, we show that all participants performance was better explained by models in which negative outcomes had minimal to no impact on learning. The performance increase over age was driven by 1) an increase in learning rate (i.e. decrease in integration time horizon); 2) a decrease in noisy/exploratory choices. In mid-adolescence age 13-15, salivary testosterone and learning rate were positively related. We discuss our findings in the context of other studies and hypotheses about adolescent brain development. Author summaryAdolescence is a time of great uncertainty. It is also a critical time for brain development, learning, and decision making in social and educational domains. There are currently contradictory findings about learning in adolescence. We sought to better isolate how learning from stable probabilistic contingencies changes during adolescence with a task that previously showed interesting results in adolescents. We collected a relatively large sample size (297 participants) across a wide age range (8-30), to trace the adolescent developmental trajectory of learning under stable but uncertain conditions. We found that age in our sample was positively associated with higher learning rates and lower choice exploration. Within narrow age bins, we found that higher saliva testosterone levels were associated with higher learning rates in participants age 13-15 years. These findings can help us better isolate the trajectory of maturation of core learning and decision making processes during adolescence.

neuroscience↗

bioRxiv2020

Understanding the Unique Advantage of Adolescents in Stochastic, Volatile Environments: Combining Reinforcement Learning and Bayesian Inference

During adolescence, youth venture out, explore the wider world, and are challenged to learn how to navigate novel and uncertain environments. We investigated whether adolescents are uniquely adapted to this transition, compared to younger children and adults. In a stochastic, volatile reversal-learning task with a sample of 291 participants aged 8-30, we found that adolescents outperformed both younger and older participants. We developed two independent cognitive models, based on Reinforcement learning (RL) and Bayesian inference (BI). The RL parameter for learning from negative outcomes and the BI parameters specifying participants mental models peaked closest to optimal in adolescents, suggesting a central role in adolescent cognitive processing. By contrast, persistence and noise parameters improved monotonously with age. We distilled the insights of RL and BI using principal component analysis and found that three shared components interacted to form the adolescent performance peak: adult-like behavioral quality, child-like time scales, and developmentally-unique processing of positive feedback. This research highlights adolescence as a neurodevelopmental window that may be specifically adapted for volatile and uncertain environments. It also shows how detailed insights can be gleaned by using cognitive models in new ways.

neuroscience↗

bioRxiv2019

Sex and pubertal status influence dendritic spine density onto frontal cortiocostriatal projection neurons

In humans, nonhuman primates, and rodents, the frontal cortices exhibit grey matter thinning and dendritic spine pruning that extends late into adolescence. This protracted maturation is believed to support higher cognition but may also confer psychiatric vulnerability during adolescence. Currently, little is known about how different cell types in the frontal cortex mature or whether puberty plays a role. Here, we used mice to characterize the spatial topography and adolescent development of cross-corticostriatal (cSTR) neurons that project to the dorsomedial striatum (DMS). We found that apical spine density on cSTR neurons in the medial prefrontal cortex decreased significantly between late juvenile (P29) and young adult time points (P60), with females exhibiting higher spine density than males at both ages. Adult males castrated prior to puberty onset had higher spine density compared to sham controls. Adult females ovariectomized before puberty onset showed greater variance in spine density measures on cSTR cells compared to controls, but their mean spine density did not significantly differ from sham controls. Our findings reveal that these cSTR neurons, a subtype of the broader class of intratelencephalic-type neurons, exhibit significant sex differences and suggest that spine pruning on cSTR neurons is regulated by puberty in males.

neuroscience↗

bioRxiv2019

Choice suppression through opponent but not independent function of the striatal indirect pathway

The dorsomedial striatum (DMS) plays a key role in action selection, but little is known about how direct and indirect pathway spiny projection neurons (dSPNs and iSPNs) contribute to choice suppression in freely moving animals. Here, we used pathway-specific chemogenetic manipulation during a serial choice foraging task to test opposing predictions for iSPN function generated by two theories: 1) the select/suppress heuristic which suggests iSPN activity is required to suppress alternate choices and 2) the network-inspired Opponent Actor Learning model (OpAL) which proposes that the weighted difference of dSPN and iSPN activity determines choice. We found that chemogenetic activation, but not inhibition, of iSPNs disrupted learned suppression of nonrewarded choices, consistent with the predictions of the OpAL model. Our findings suggest that iSPNs role in stopping and freezing does not extend in a simple fashion to choice suppression. These data may provide insights critical for the successful design of interventions for addiction or other conditions in which suppression of behavior is desirable.

neuroscience↗

bioRxiv2019

Prepubertal gonadectomy reveals sex differences in approach-avoidance behavior in adult mice

Adolescence is a developmental period that is associated with physical, cognitive, and affective maturation and a time when sex biases in multiple psychiatric diseases emerge. While puberty onset marks the initiation of adolescence, it is unclear whether the pubertal rise in gonadal hormones generates sex differences in approach-avoidance behaviors that may impact psychiatric vulnerability. To examine the influence of peripubertal gonadal hormone exposure on adult behavior, we removed the gonads or performed sham surgery in male and female mice just prior to puberty onset and assessed performance in an odor-guided foraging task and anxiety-related behaviors in adulthood. We observed no significant sex differences in foraging or anxiety-related behaviors between intact adult male and female mice but found significant differences between adult male and female mice that had been gonadectomized (GDX) prior to puberty. GDX males failed to acquire the odor-guided foraging task, showed reduced locomotion, and exhibited increased anxiety-like behavior, while GDX females showed the opposite pattern of behavior. These data suggest that similar approach-avoidance phenotypes are achieved in male and female mice via different mechanisms mediated by the sex-specific hormonal milieus during pubertal maturation.

animal behavior and cognition↗

bioRxiv2019

Distentangling the systems contributing to changes in learning during adolescence

Multiple neurocognitive systems contribute simultaneously to learning. For example, dopamine and basal ganglia (BG) systems are thought to support reinforcement learning (RL) by incrementally updating the value of choices, while the prefrontal cortex (PFC) contributes different computations, such as actively maintaining precise information in working memory (WM). It is commonly thought that WM and PFC show more protracted development than RL and BG systems, yet their contributions are rarely assessed in tandem. Here, we used a simple learning task to test how RL and WM contribute to changes in learning across adolescence. We tested 187 subjects ages 8 to 17 and 53 adults (25-30). Participants learned stimulus-action associations from feedback; the learning load was varied to be within or exceed WM capacity. Participants age 8-12 learned slower than participants age 13-17, and were more sensitive to load. We used computational modeling to estimate subjects use of WM and RL processes. Surprisingly, we found more robust changes in RL than WM during development. RL learning rate increased significantly with age across adolescence and WM parameters showed more subtle changes, many of them early in adolescence. These results underscore the importance of changes in RL processes for the developmental science of learning.\n\nHighlights- Subjects combine reinforcement learning (RL) and working memory (WM) to learn\n- Computational modeling shows RL learning rates grew with age during adolescence\n- When load was beyond WM capacity, weaker RL compensated less in younger adolescents\n- WM parameters showed subtler and more puberty-related changes\n- WM reliance, maintenance, and capacity had separable developmental trajectories\n- Underscores importance of RL processes in developmental changes in learning

neuroscience↗