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Tue, 17 Oct 2023 19:00:01 GMT

New work from @emiwright.bsky.social in PNAS shows how androgens act during pubertal development to program behavioral and neural responses to stress https://www.pnas.org/doi/10.1073/pnas.2306475120

We knew for 10 yrs that defeat stress had stronger effects on social behavior in females vs males but did not know why; Emily solved it by showing that males and females are equally sensitive to stress before puberty https://www.pnas.org/doi/10.1073/pnas.2306475120#fig01

She showed that removing the testes from males before puberty made more sensitive to stress as adults. There was no effect hormones without stress https://www.pnas.org/doi/10.1073/pnas.2306475120#fig02

Emily then imported fiber photometry to the lab working with Lin Tian's group. With help from @hczakharenkov.bsky.social they used @deeplabcut.bsky.social to track mice during calcium imaging https://www.pnas.org/doi/10.1073/pnas.2306475120#fig03

Emily imaged the ventral BNST in males assigned to prepubertal castration or sham surgery, and the exposed the mice to stress as adults. Hannah's analysis (with help from Drew Fox) showed stronger GCaMP signals when these mice interacted with target mice

Emily had the idea to have focal mice interact with aggressive or non-aggressive target mice. Sham and castrated males showed big increases in BNST activity when interacting with aggressive target mice

However, with nonaggressive mice, only castrated males showed an increase in BNST activity. This suggests that castrated males may overgeneralize threats after stress exposure

This exciting result made us wonder how the BNST responded without stress exposure. With help from @peiluo@bsky.social we imaged the BNST of intact males before and after stress https://www.pnas.org/doi/10.1073/pnas.2306475120#fig04

As Emily said, the exp had a different vibe. When focal males are not stressed, they are aggressive with target mice. When target mice fought back, there was increased activity in the BNST, consistent with the theme of BNST responding to threat

We also looked to see how puberty affected the oxytocin system. Prepubertal castration increased c-fos in the PVN oxytocin neurons and BNST. These analyses led by Alexandra Serna Godoy, who is applying to grad school now https://www.pnas.org/doi/10.1073/pnas.2306475120#fig05

The final piece was identifying the hormonal mechanism. During the pandemic I taught Emily how to make silastic implants using a GoPro bc only one person could be in lab at a time

Emily showed that testosterone or dihydrotestosterone replacement during puberty reduced effects of stress in adults. Since DHT can't be converted into estrogens this implicates androgen receptors as a key mechanism. https://www.pnas.org/doi/10.1073/pnas.2306475120#fig06

With help from Zhana Prince and Alyssa Lake we examined how DHT during puberty affected females. DHT also blunted effects of stress in females. A key observation was DHT had no effect in females without stress exposure

I'm so proud of Emily. I did not want to do a developmental study but she fought for it and solved a decade long question for our model. Her work opens many new doors for studying pubertal development.

Tue, 17 Oct 2023 18:55:09 GMT

New work from @emiwright.bsky.social in PNAS shows how androgens act during pubertal development to program behavioral and neural responses to stress https://www.pnas.org/doi/10.1073/pnas.2306475120

However, with nonaggressive mice, only castrated males showed an increase in BNST activity. This suggests that castrated males may overgeneralize threats after stress exposure

The final piece was identifying the hormonal mechanism. During the pandemic I taught Emily how to make silastic implants using a GoPro bc only one person could be in lab at a time

Tue, 17 Oct 2023 18:54:39 GMT

New work from @emiwright.bsky.social in PNAS shows how androgens act during pubertal development to program behavioral and neural responses to stress https://www.pnas.org/doi/10.1073/pnas.2306475120

However, with nonaggressive mice, only castrated males showed an increase in BNST activity. This suggests that castrated males may overgeneralize threats after stress exposure

The final piece was identifying the hormonal mechanism. During the pandemic I taught Emily how to make silastic implants using a GoPro bc only one person could be in lab at a time