Biology subjects

Drzewiecki, C. M.

Publications and source records attributed to Drzewiecki, C. M..

4 recordsLinked to original sources

bioRxiv2026

Extended amygdala function is governed by threat probability, not uncertainty

Anxiety is a universal experience that arises as we anticipate negative events that may or may not happen. When extreme, anxiety is a major cause of distress, suffering, and disability-adjusted life years, with nearly one in four individuals experiencing clinically relevant anxiety in their lifetime1-3. Elucidating the biological basis of anxiety has the potential to help people understand, cope with, and ultimately receive improved treatments for their anxiety. The canonical neuroscientific model of anxiety posits that distinct regions of the extended amygdala (EA) elicit distress that is conditional on threat uncertainty4. Here, we refute this model using a precise computational framework to disambiguate specific dimensional facets of threat uncertainty in a racially diverse sample of 104 individuals. We show that self-report, psychophysiological, and neural correlates of threat anticipation are much more strongly associated with threat probability than uncertainty per se. Importantly, EA regions, including the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST), were most reliably associated with threat probability--contrary to the canonical model. Re-examination of the pioneering experiments that motivated the canonical model reveal a previously unappreciated confound between probability and uncertainty, suggesting the novel hypothesis that EA regions differ in their sensitivity to low-probability threats. Our fMRI data support this, showing that BST is more sensitive to low-probability threats than Ce. Moreover, lesion experiments in rhesus monkeys (Macaca mulatta) demonstrate that BST causally contributes to defensive behavior in low-probability threat contexts. Together, these data reconcile previous empirical inconsistencies, provide a fresh theoretical perspective on the neurobiology of anxiety, and underscore the theoretical importance of a formal lingua franca for coordinated cross-species emotion research.

neuroscience↗

bioRxiv2024

Brain Charts for the Rhesus Macaque Lifespan

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

neuroscience↗

bioRxiv2021

Impact of pubertal onset on region-specific Esr2 expression

In female rats, pubertal onset is associated with maturation of the medial prefrontal cortex (mPFC) and mPFC-mediated behaviors. These behavioral and anatomical changes are likely due to effects of estrogen at the nuclear estrogen receptor beta (ER{beta}), which is expressed at higher levels than the estrogen receptor alpha (ER) isoform in the adult mPFC. Researchers have previously quantified ER{beta} protein and Esr2 RNA in rodents during early postnatal development and adulthood, but an adolescent-specific trajectory of this receptor in the mPFC has not been documented. Given that levels of Esr2 can fluctuate in the presence or absence of estrogens, puberty and the subsequent rise in gonadal hormones could influence ER{beta} expression in the adolescent brain. To further explore this, we used RNAscope to quantify the amount of Esr2 mRNA in pre-pubertal adolescent, recently post-pubertal adolescent, and adult female rats. We show here that Esr2 expression decreases significantly in the mPFC, striatum and motor cortex between pre-pubertal adolescence and adulthood. In the mPFC, this decrease occurs rapidly at pubertal onset, with no significant decrease in Esr2 levels between the recently post-pubertal and adult cohort. In contrast in the striatum and motor cortex, there were no significant differences in the amount of Esr2 between pre- and post-pubertal females. Insofar as the amount of Esr2 is proportional to functional ER{beta}, these results suggest ER{beta} decreases in a region-specific pattern in response to pubertal onset and highlight a role for this receptor in the maturational events that occur in the female rat mPFC at puberty.

neuroscience↗

bioRxiv2020

Influences of age and pubertal status on number of perineuronal nets in the rat medial prefrontal cortex

The prefrontal cortex (PFC) is a late developing region of the cortex, and its protracted maturation during adolescence may confer a period of plasticity. Closure of critical, or sensitive, periods in sensory cortices coincides with perineuronal net (PNN) expression, leading to enhanced inhibitory function and synaptic stabilization. PNN density is known to increase across adolescence in the male rodent medial PFC (mPFC). However, the trajectory of female PNN development has not been explored nor has the potential role of pubertal onset in PNN expression. Here, we examined rats at four time points spanning adolescent development to quantify the number of PNNs in the mPFC, as well as the total volume of the prefrontal white matter. Additionally, because puberty coincides with broad behavioral and neuroanatomical changes, we collected tissue from age-matched pre- and post- pubertal siblings within a litter. Results indicate that both males and females show an increase the total number of mPFC PNNs and in white matter under the mPFC between postnatal day (P) 30 and P60. Male puberty did not affect PNNs, while female pubertal onset led to an abrupt decrease in the total number of PNNs that persisted through mid-adolescence before increasing at P60. This decrease in female rats may indicate a difference in timing of maximal plasticity between the sexes during adolescence.

neuroscience↗