Chronic Variable Mild Stress Alters Avoidance Behavior in Mice but has no Influence on the Transcriptome of the Anterodorsal Bed Nucleus of the Stria Terminalis and the M-Current of NPY Neurons

Degroat, Thomas, Wiersielis, Kimberly, Denny, Katherine, Tollkuhn, Jessica, Samuels, Benjamin A, Roepke, Troy (2022) Chronic Variable Mild Stress Alters Avoidance Behavior in Mice but has no Influence on the Transcriptome of the Anterodorsal Bed Nucleus of the Stria Terminalis and the M-Current of NPY Neurons. In: ACNP 61st Annual Meeting.


Background: In humans, chronic stress leads to the development of mood disorders such as major depressive disorder and post-traumatic stress disorder. It has also been shown that women are more susceptible to the development of these disorders, suggesting a sex-related difference in how we process stress. The anterodorsal bed nucleus of the stria terminalis (abBNST) is a brain region that is essential for the central stress response. It is considered a part of the extended amygdala and serves as a relay between the amygdala and the prefrontal cortex. This region also has sexually dimorphic in expression of aromatase and estrogen receptors. Therefore, the adBNST may play a major role in the sex difference observed. We have previously demonstrated that chronic stress alters corticotropin-releasing hormone (CRH) expression and the M-current, a potassium current, in CRH neurons in the BNST from male mice. Other BNST neurons express Neuropeptide Y (NPY) which may plays a role in the stress response. We hypothesized that the CVMS paradigm would results in alterations in behavior of both male and female mice, sex-dependent differences in the transcriptome, and that adBNST NPY neurons would be affected by chronic stress, leading to a decreased M-current. Methods: To study the effects of chronic stress on the adBNST, we used both wild-type and NPY-GFP male and female mice. Mice experienced six weeks of a chronic variable mild stress (CVMS) paradigm or no stress prior to behavior testing, adBNST tissue collection for RNA sequencing, and whole-cell patch clamp electrophysiology. The behavior tests conducted were the open field test (OFT), elevated plus maze (EPM), light dark box (LDB), and novelty suppressed feeding (NSF). Results: Our results show that stress did cause sex-dependent differences in behavior depending on the parameters of the test. In the OFT, CVMS mice spent less time in the center (main effect of stress P = .0019) and more time in the corners (main effect of stress P = .0209). In the EPM, CVMS exposed mice spent more time in the closed arms than controls (main effect of stress P = .0011) and females had more open arm crossings than males. In the LDB, no effects were observed other than male mice had more stretch attend postures than females (main effect of stress P = .0377; interaction P = .0002). In the NSF, no effects were observed except that stressed mice weighed less than non-stressed mice (main effect of stress P = .0136). Serum corticosterone levels are currently being analyzed from blood collected before and after stress. RNA sequencing of the adBNST from stressed and unstressed mice found no effects of stress on any gene, potentially due to high variability between samples, but did find differences in expression between the sexes for ~30 genes. CVMS exposure did not affect neuronal excitability or the M-current in the adBNST NPY neurons, nor was there a sex-related difference. There was no effect on resting membrane potential yet there was an effect of stress on input resistance (P = .0286). The max peak of the M-current in control males was 30.4 pA, in stress males max peak was 34.0 pA (t-test: P = 0.5175), in females, control max peak was 23.4 pA, and stress max peak was 26.8 pA (t-test: P = 0.6979). Conclusions: Our data suggests that CVMS is an effector of behavior in mice, but that adBNST NPY neurons may not be an important regulator of chronic stress or a mediator of the sex differences in the response to chronic stress.

Item Type: Conference or Workshop Item (Poster)
Subjects: organism description > animal behavior > sex differences
organism description > animal behavior > stress
CSHL Authors:
Communities: CSHL labs > Tollkuhn lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 2022
Date Deposited: 12 Oct 2023 19:19
Last Modified: 12 Oct 2023 19:19
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