@article{RN21,

title = {Imaging striatal dopamine release using a nongenetically encoded near infrared fluorescent catecholamine nanosensor},

author = {A. G. Beyene and K. Delevich and J. T. Del Bonis-O'Donnell and D. J. Piekarski and W. C. Lin and A. W. Thomas and S. J. Yang and P. Kosillo and D. Yang and G. S. Prounis and L. Wilbrecht and M. P. Landry},

doi = {10.1126/sciadv.aaw3108},

issn = {2375-2548},

year  = {2019},

date = {2019-01-01},

journal = {Science Advances},

volume = {5},

number = {7},

pages = {eaaw3108},

abstract = {Neuromodulation plays a critical role in brain function in both health and disease, and new tools that capture neuromodulation with high spatial and temporal resolution are needed. Here, we introduce a synthetic catecholamine nanosensor with fluorescent emission in the near infrared range (1000–1300 nm), near infrared catecholamine nanosensor (nIRCat). We demonstrate that nIRCats can be used to measure electrically and optogenetically evoked dopamine release in brain tissue, revealing hotspots with a median size of 2 µm. We also demonstrated that nIRCats are compatible with dopamine pharmacology and show D2 autoreceptor modulation of evoked dopamine release, which varied as a function of initial release magnitude at different hotspots. Together, our data demonstrate that nIRCats and other nanosensors of this class can serve as versatile synthetic optical tools to monitor neuromodulatory neurotransmitter release with high spatial resolution.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN23,

title = {Neuroscience: Sex Hormones at Work in the Neocortex},

author = {K. Delevich and D. Piekarski and L. Wilbrecht},

doi = {10.1016/j.cub.2019.01.013},

issn = {0960-9822},

year  = {2019},

date = {2019-01-01},

journal = {Current Biology},

volume = {29},

number = {4},

pages = {R122-r125},

abstract = {Sex hormones have easy access to the brain and their receptors are expressed by cortical neurons. Until recently, little was known about what impact, if any, they have on cortical processing. New data reveal that estradiol potently alters inhibitory neurotransmission in the neocortex.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN22,

title = {Adolescence and "Late Blooming" Synapses of the Prefrontal Cortex},

author = {K. Delevich and A. W. Thomas and L. Wilbrecht},

doi = {10.1101/sqb.2018.83.038828},

issn = {0091-7451},

year  = {2019},

date = {2019-01-01},

journal = {Cold Spring Harb Symp Quant Biol},

abstract = {The maturation of the prefrontal cortex (PFC) during adolescence is thought to be important for cognitive and affective development and mental health risk. Whereas many summaries of adolescent development have focused on dendritic spine pruning and gray matter thinning in the PFC during adolescence, we highlight recent rodent data from our laboratory and others to call attention to continued synapse formation and plasticity in the adolescent period in specific cell types and circuits. In particular, we highlight changes in inhibitory neurotransmission onto intratelencephalic (IT-type) projecting cortical neurons and late expansion of connectivity between the amygdala and PFC and the ventral tegmental area and PFC. Continued work on these “late blooming” synapses in specific cell types and circuits, and their interrelationships, will illuminate new opportunities for understanding and shaping the biology of adolescent development. We also address which aspects of adolescent PFC development are dependent on pubertal processes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{delevichComingofage,

title = {Coming of age in the frontal cortex: The role of puberty in cortical maturation},

author = {K. Delevich and M. Klinger and N. J. Okada and L. Wilbrecht},

url = {https://doi.org/10.1016/j.semcdb.2021.04.021},

doi = {10.1016/j.semcdb.2021.04.021},

issn = {0091-7451},

year  = {2019},

date = {2019-01-01},

journal = {Seminars in Cell and Developmental Biology},

volume = {118},

pages = {64-72},

abstract = {Across species, adolescence is a period of growing independence that is associated with the maturation of cognitive, social, and affective processing. Reorganization of neural circuits within the frontal cortex is believed to contribute to the emergence of adolescent changes in cognition and behavior. While puberty coincides with adolescence, relatively little is known about which aspects of frontal cortex maturation are driven by pubertal development and gonadal hormones. In this review, we highlight existing work that suggests puberty plays a role in the maturation of specific cell types in the medial prefrontal cortex (mPFC) of rodents, and highlight possible routes by which gonadal hormones influence frontal cortical circuit development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Delevich638916,

title = {Prepubertal gonadectomy reveals sex differences in approach-avoidance behavior in adult mice},

author = {Kristen Delevich and Christopher Hall and Josiah R. Boivin and David Piekarski and Yuting Zhang and Linda Wilbrecht},

url = {https://www.biorxiv.org/content/early/2019/05/28/638916},

year  = {2019},

date = {2019-01-01},

journal = {Hormones and Behavior},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{thomasvariation2019,

title = {Variation in early life maternal care predicts later long range frontal cortex synapse development in mice},

author = {A. Wren Thomas and Kristen Delevich and Irene Chang and Linda Wilbrecht},

url = {http://www.sciencedirect.com/science/article/pii/S187892931930324X},

doi = {https://doi.org/10.1016/j.dcn.2019.100737},

issn = {1878-9293},

year  = {2019},

date = {2019-01-01},

journal = {Developmental Cognitive Neuroscience},

pages = {100737},

abstract = {Empirical and theoretical work suggests that early postnatal experience may inform later developing synaptic connectivity to adapt the brain to its environment. We hypothesized that early maternal experience may program the development of synaptic density on long range frontal cortex projections. To test this idea, we used maternal separation (MS) to generate environmental variability and examined how MS affected 1) maternal care and 2) synapse density on virally-labeled long range axons of offspring reared in MS or control conditions. We found that MS and variation in maternal care predicted bouton density on dorsal frontal cortex axons that terminated in the basolateral amygdala (BLA) and dorsomedial striatum (DMS) with more, fragmented care associated with higher density. The effects of maternal care on these distinct axonal projections of the frontal cortex were manifest at different ages. Maternal care measures were correlated with frontal cortex → BLA bouton density at mid-adolescence postnatal (P) day 35 and frontal cortex → DMS bouton density in adulthood (P85). Meanwhile, we found no evidence that MS or maternal care affected bouton density on ascending orbitofrontal cortex (OFC) or BLA axons that terminated in the dorsal frontal cortices. Our data show that variation in early experience can alter development in a circuit-specific and age-dependent manner that may be relevant to early life adversity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{masterdistentangling2019,

title = {Distentangling the systems contributing to changes in learning during adolescence},

author = {Sarah L. Master and Maria K. Eckstein and Neta Gotlieb and Ronald Dahl and Linda Wilbrecht and Anne G. E. Collins},

url = {http://www.sciencedirect.com/science/article/pii/S1878929319303196},

doi = {https://doi.org/10.1016/j.dcn.2019.100732},

issn = {1878-9293},

year  = {2019},

date = {2019-01-01},

journal = {Developmental Cognitive Neuroscience},

pages = {100732},

abstract = {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 protracted changes in RL than WM during development. RL learning rate increased with age until age 18 and WM parameters showed more subtle, gender- and puberty-dependent changes early in adolescence. These results can inform education and intervention strategies based on the developmental science of learning.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN27,

title = {Adolescent pruning and stabilization of dendritic spines on cortical layer 5 pyramidal neurons do not depend on gonadal hormones},

author = {J. R. Boivin and D. J. Piekarski and A. W. Thomas and L. Wilbrecht},

doi = {10.1016/j.dcn.2018.01.007},

issn = {1878-9293},

year  = {2018},

date = {2018-01-01},

journal = {Developmental Cognitive Neuroscience},

volume = {30},

pages = {100-107},

abstract = {Pyramidal neurons in the neocortex receive a majority of their synapses on dendritic spines, whose growth, gain, and loss regulate the strength and identity of neural connections. Juvenile brains typically show higher spine density and turnover compared to adult brains, potentially enabling greater capacity for experience-dependent circuit ‘rewiring’. Although spine pruning and stabilization in frontal cortex overlap with pubertal milestones, it is unclear if gonadal hormones drive these processes. To address this question, we used hormone manipulations and in vivo 2-photon microscopy to test for a causal relationship between pubertal hormones and spine pruning and stabilization in layer 5 neurons in the frontal cortex of female mice. We found that spine density, gains, and losses decreased from P27 to P60 and that these measures were not affected by pre-pubertal hormone injections or ovariectomy. Further analyses of spine morphology after manipulation of gonadal hormones suggest that gonadal hormones may play a role in morphological maturation and dynamics. Our data help to segregate hormone-sensitive and hormone-insensitive maturational processes that occur simultaneously in dorsomedial frontal cortex. These data provide more specific insight into adolescent development and may have implications for understanding the neurodevelopmental effects of changes in pubertal timing in humans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN26,

title = {Importance of investing in adolescence from a developmental science perspective},

author = {R. E. Dahl and N. B. Allen and L. Wilbrecht and A. B. Suleiman},

doi = {10.1038/nature25770},

issn = {0028-0836},

year  = {2018},

date = {2018-01-01},

journal = {Nature},

volume = {554},

number = {7693},

pages = {441-450},

abstract = {This review summarizes the case for investing in adolescence as a period of rapid growth, learning, adaptation, and formational neurobiological development. Adolescence is a dynamic maturational period during which young lives can pivot rapidly—in both negative and positive directions. Scientific progress in understanding adolescent development provides actionable insights into windows of opportunity during which policies can have a positive impact on developmental trajectories relating to health, education, and social and economic success. Given current global changes and challenges that affect adolescents, there is a compelling need to leverage these advances in developmental science to inform strategic investments in adolescent health.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN24,

title = {Adolescence and "Late Blooming" Synapses of the Prefrontal Cortex},

author = {K. Delevich and A. W. Thomas and L. Wilbrecht},

doi = {10.1101/sqb.2018.83.037507},

issn = {0091-7451},

year  = {2018},

date = {2018-01-01},

journal = {Cold Spring Harb Symp Quant Biol},

volume = {83},

pages = {37-43},

abstract = {The maturation of the prefrontal cortex (PFC) during adolescence is thought to be important for cognitive and affective development and mental health risk. Whereas many summaries of adolescent development have focused on dendritic spine pruning and gray matter thinning in the PFC during adolescence, we highlight recent rodent data from our laboratory and others to call attention to continued synapse formation and plasticity in the adolescent period in specific cell types and circuits. In particular, we highlight changes in inhibitory neurotransmission onto intratelencephalic (IT-type) projecting cortical neurons and late expansion of connectivity between the amygdala and PFC and the ventral tegmental area and PFC. Continued work on these “late blooming” synapses in specific cell types and circuits, and their interrelationships, will illuminate new opportunities for understanding and shaping the biology of adolescent development. We also address which aspects of adolescent PFC development are dependent on pubertal processes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN25,

title = {Mice engineered to mimic a common Val66Met polymorphism in the BDNF gene show greater sensitivity to reversal in environmental contingencies},

author = {A. Vandenberg and W. C. Lin and L. H. Tai and D. Ron and L. Wilbrecht},

doi = {10.1016/j.dcn.2018.05.009},

issn = {1878-9293},

year  = {2018},

date = {2018-01-01},

journal = {Developmental Cognitive Neuroscience},

volume = {34},

pages = {34-41},

abstract = {A common human polymorphism in the gene that encodes brain derived neurotrophic factor (BDNF), Val66Met, is considered a marker of vulnerability for mental health issues and has been associated with cognitive impairment. An alternate framework has been proposed in which “risk alleles” are reinterpreted as “plasticity alleles” that confer vulnerability in adverse environments and positive effects in neutral or positive environments (Belsky et al., 2009). These frameworks produce divergent predictions for tests of learning and cognitive flexibility. Here, we examined multiple aspects of learning and cognitive flexibility in a relatively new BDNF Val66Met mouse model (BDNF Val68Met, Warnault et al., 2016), including multiple choice discrimination and reversal, go/no-go learning and reversal, and appetitive extinction learning. We found that mice homozygous for the Met allele show more efficient reversal learning in two different paradigms, but learn at rates comparable to Val homozygotes on the multiple choice discrimination task, a go/no-go task, and in appetitive extinction. Our results dissociate reversal performance from go/no-go learning and appetitive extinction and support the plasticity allele framework that suggests BDNF Met carriers are potentially more sensitive to changes in the environment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN28,

title = {Age, sex, and gonadal hormones differently influence anxiety- and depression-related behavior during puberty in mice},

author = {J. R. Boivin and D. J. Piekarski and J. K. Wahlberg and L. Wilbrecht},

doi = {10.1016/j.psyneuen.2017.08.009},

issn = {0306-4530},

year  = {2017},

date = {2017-01-01},

journal = {Psychoneuroendocrinology},

volume = {85},

pages = {78-87},

abstract = {Anxiety and depression symptoms increase dramatically during adolescence, with girls showing a steeper increase than boys after puberty onset. The timing of the onset of this sex bias led us to hypothesize that ovarian hormones contribute to depression and anxiety during puberty. In humans, it is difficult to disentangle direct effects of gonadal hormones from social and environmental factors that interact with pubertal development to influence mental health. To test the role of gonadal hormones in anxiety- and depression-related behavior during puberty, we manipulated gonadal hormones in mice while controlling social and environmental factors. Similar to humans, we find that mice show an increase in depression-related behavior from pre-pubertal to late-pubertal ages, but this increase is not dependent on gonadal hormones and does not differ between sexes. Anxiety-related behavior, however, is more complex during puberty, with differences that depend on sex, age, behavioral test, and hormonal status. Briefly, males castrated before puberty show greater anxiety-related behavior during late puberty compared to intact males, while pubertal females are unaffected by ovariectomy or hormone injections in all assays except the marble burying test. Despite this sex-specific effect of pubertal hormones on anxiety-related behavior, we find no sex differences in intact young adults, suggesting that males and females use separate mechanisms to converge on a similar behavioral phenotype. Our results are consistent with anxiolytic effects of testicular hormones during puberty in males but are not consistent with a causal role for ovarian hormones in increasing anxiety- and depression-related behavior during puberty in females.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN29,

title = {Ovarian Hormones Organize the Maturation of Inhibitory Neurotransmission in the Frontal Cortex at Puberty Onset in Female Mice},

author = {D. J. Piekarski and J. R. Boivin and L. Wilbrecht},

doi = {10.1016/j.cub.2017.05.027},

issn = {0960-9822},

year  = {2017},

date = {2017-01-01},

journal = {Current Biology},

volume = {27},

number = {12},

pages = {1735-1745.e3},

abstract = {The frontal cortex matures late in development, showing dramatic changes after puberty onset, yet few experiments have directly tested the role of pubertal hormones in cortical maturation. One mechanism thought to play a primary role in regulating the maturation of the neocortex is an increase in inhibitory neurotransmission, which alters the balance of excitation and inhibition. We hypothesized that pubertal hormones could regulate maturation of the frontal cortex by this mechanism. Here, we report that manipulations of gonadal hormones do significantly alter the maturation of inhibitory neurotransmission in the cingulate region of the mouse medial frontal cortex, an associative region that matures during the pubertal transition and is implicated in decision making, learning, and psychopathology. We find that inhibitory neurotransmission, but not excitatory neurotransmission, increases onto cingulate pyramidal neurons during peri-pubertal development and that this increase can be blocked by pre-pubertal, but not post-pubertal, gonadectomy. We next used pre-pubertal hormone treatment to model early puberty onset, a phenomenon increasingly observed in girls living in developed nations. We find that pre-pubertal hormone treatment drives an early increase in inhibitory neurotransmission in the frontal cortex, but not the somatosensory cortex, suggesting that earlier puberty can advance cortical maturation in a regionally specific manner. Pre-pubertal hormone treatment also accelerates maturation of tonic inhibition and performance in a frontal-cortex-dependent reversal-learning task. These data provide rare evidence of enduring, organizational effects of ovarian hormones at puberty and provide a potential mechanism by which gonadal hormones could regulate the maturation of the associative neocortex.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN32,

title = {Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex?},

author = {D. J. Piekarski and C. M. Johnson and J. R. Boivin and A. W. Thomas and W. C. Lin and K. Delevich and M. Galarce E and L. Wilbrecht},

doi = {10.1016/j.brainres.2016.08.042},

issn = {0006-8993},

year  = {2017},

date = {2017-01-01},

journal = {Brain Research},

volume = {1654},

number = {Pt B},

pages = {123-144},

abstract = {Postnatal brain development is studded with sensitive periods during which experience dependent plasticity is enhanced. This enables rapid learning from environmental inputs and reorganization of cortical circuits that matches behavior with environmental contingencies. Significant headway has been achieved in characterizing and understanding sensitive period biology in primary sensory cortices, but relatively little is known about sensitive period biology in associative neocortex. One possible mediator is the onset of puberty, which marks the transition to adolescence, when animals shift their behavior toward gaining independence and exploring their social world. Puberty onset correlates with reduced behavioral plasticity in some domains and enhanced plasticity in others, and therefore may drive the transition from juvenile to adolescent brain function. Pubertal onset is also occurring earlier in developed nations, particularly in unserved populations, and earlier puberty is associated with vulnerability for substance use, depression and anxiety. In the present article we review the evidence that supports a causal role for puberty in developmental changes in the function and neurobiology of the associative neocortex. We also propose a model for how pubertal hormones may regulate sensitive period plasticity in associative neocortex. We conclude that the evidence suggests puberty onset may play a causal role in some aspects of associative neocortical development, but that further research that manipulates puberty and measures gonadal hormones is required. We argue that further work of this kind is urgently needed to determine how earlier puberty may negatively impact human health and learning potential.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN34,

title = {Long-range orbitofrontal and amygdala axons show divergent patterns of maturation in the frontal cortex across adolescence},

author = {C. M. Johnson and F. A. Loucks and H. Peckler and A. W. Thomas and P. H. Janak and L. Wilbrecht},

doi = {10.1016/j.dcn.2016.01.005},

issn = {1878-9293},

year  = {2016},

date = {2016-01-01},

journal = {Developmental Cognitive Neuroscience},

volume = {18},

pages = {113-20},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN33,

title = {Rule learning enhances structural plasticity of long-range axons in frontal cortex},

author = {C. M. Johnson and H. Peckler and L. H. Tai and L. Wilbrecht},

doi = {10.1038/ncomms10785},

issn = {2041-1723},

year  = {2016},

date = {2016-01-01},

journal = {Nature Communications},

volume = {7},

pages = {10785},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN31,

title = {Risky decision-making in adolescent girls: The role of pubertal hormones and reward circuitry},

author = {Z. A. Op de Macks and S. A. Bunge and O. N. Bell and L. Wilbrecht and L. J. Kriegsfeld and A. S. Kayser and R. E. Dahl},

doi = {10.1016/j.psyneuen.2016.08.013},

issn = {0306-4530},

year  = {2016},

date = {2016-01-01},

journal = {Psychoneuroendocrinology},

volume = {74},

pages = {77-91},

keywords = {},

pubstate = {published},

tppubtype = {article}

}