Pubmed: Wilbrecht L
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.
Kristen Delevich, David Piekarski, Linda Wilbrecht, Neuroscience: Sex Hormones at Work in the Neocortex,
29(4) Current Biology R122–R125 (2019) https://doi.org/10.1016/j.cub.2019.01.013, http://www.sciencedirect.com/science/article/pii/S0960982219300156
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 […]
Mice engineered to mimic a common Val66Met polymorphism in the BDNF gene show greater sensitivity to reversal in environmental contingencies
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), […]
Imaging Striatal Dopamine Release Using a Non-Genetically Encoded Near-Infrared Fluorescent Catecholamine Nanosensor
Neuromodulation plays a critical role in brain function in both health and disease. New optical tools, and their validation in biological tissues, are needed that can image neuromodulation with high spatial and temporal resolution, which will add an important new dimension of information to neuroscience research. Here, we demonstrate the use of a catecholamine nanosensor with fluorescent emission in the 1000-1300 nm near-infrared window to measure dopamine transmission in ex vivo brain slices. These near-infrared catecholamine nanosensors (nIRCats) represent a broader class of nanosensors that can be synthesized from non-covalent conjugation of single wall carbon nanotubes (SWNT) with single strand oligonucleotides. […]
Professor Wilbrecht’s essay, Your Twelve-Year-Old Isn’t Just Sprouting New Hair but Is Also Forming (and Being Formed by) New Neural Connections, appears in Think Tank: Forty Neuroscientists Explore the Biological Roots of Human Experience (David J. Linden, ed. 2018).
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.
Ronald E. […]
Age, sex, and gonadal hormones differently influence anxiety- and depression-related behavior during puberty in mice
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 […]
Ovarian Hormones Organize the Maturation of Inhibitory Neurotransmission in the Frontal Cortex at Puberty Onset in Female Mice
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 […]
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 […]
Long-range orbitofrontal and amygdala axons show divergent patterns of maturation in the frontal cortex across adolescence
The adolescent transition from juvenile to adult is marked by anatomical and functional remodeling of brain networks. Currently, the cellular and synaptic level changes underlying the adolescent transition are only coarsely understood. Here, we use two-photon imaging to make time-lapse observations of long-range axons that innervate the frontal cortex in the living brain. We labeled cells in the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) and imaged their axonal afferents to the dorsomedial prefrontal cortex (dmPFC). We also imaged the apical dendrites of dmPFC pyramidal neurons. Images were taken daily in separate cohorts of juvenile (P24–P28) and young adult mice (P64–P68), […]