two-color-multifiber-photometry-recordings-social-behavior-network

Two-color Multifiber Photometry Recordings of the Social Behavior Network in Mice

Fiber photometry, the bulk recording of signals through a fiber optic cable, is a useful method for recording calcium activity from groups of neurons in ...

Princeton University

Major depressive disorder is one of the most commonly diagnosed mental illnesses worldwide, with a higher prevalence in women than in men. Although currently available pharmacological therapeutics help many individuals, they are not effective for most. Animal models have been important for the discovery of molecular alterations in stress and depression, but difficulties in adapting animal models of depression for females has impeded progress in developing novel therapeutic treatments that may be more efficacious for women.

Comparative Transcriptional Analyses in the Nucleus Accumbens Identifies RGS2 as a Key Mediator of Depression-Related Behavior.

Estrogens are inherently dynamic signaling molecules whose fluctuations induce profound shifts in physiology and behavior. However, methods for tracking the dynamics of estrogen action  are limited and not tissue-specific, making it difficult to directly relate dynamics to ongoing physiological, behavioral, and neural changes. Traditionally, estrogen sensitive cells have been identified by metrics such as receptor expression or radioactive ligand binding, but these measures do not capture the dynamic nature of hormone response. In addition, current methods for assessing the dynamics of estrogens in an individual, including microdialysis and vaginal cytology, lack temporal and spatial resolution. To address this need we developed a bifunctional reporter called neuro-seeER (neuronal see Estrogen Response) that can be used to track changes in exogenous and endogenous estrogen dynamics  and  including longitudinally in behaving animals. We confirmed that the fluorescent response requires estrogen receptor expression, is specific to activation with estradiol, and is consistent with the timescale of transcriptional induction. Neuro-seeER expression in the hypothalamus of Esr1-Cre mice revealed dynamic labeling of estrogen-responsive cells following treatment with exogenous estradiol, and fluorescence-aided cell sorting followed by RNA-sequencing confirmed that high neuro-seeER response is associated with enriched expression of genes associated with endogenous estrogen responses. Using a novel "snapshot" photometry method to track the dynamics longitudinally  we demonstrate that we can robustly detect exogenous estrogen response across multiple hypothalamic sites simultaneously. Finally, we demonstrate that this tool is uniquely suited to capturing endogenous estrogen response dynamics  across the long timescale of the estrous cycle, revealing individual differences in neural estrogen dynamics. Together, these findings reveal unexpected cellular and temporal heterogeneity of the transcriptional response and demonstrate the feasibility of tracking the dynamics of hormonal response alongside additional neural, cell signaling, or behavioral measures.

A bifunctional optical reporter for tracking estrogen response dynamics in neurons.

Frontotemporal dementia (FTD) can cause cognitive impairments and disrupt the ability to perceive others' emotions. We examined whether cognitive impairments in semantic knowledge and executive function are related to two aspects of emotion perception. Individuals with FTD and healthy controls ( = 110; 33 behavioral variant FTD, 23 non-fluent variant FTD, 30 semantic variant FTD, and 24 controls) completed neuropsychological tests of semantic word knowledge (Peabody Picture Vocabulary, Boston Naming Tests) and executive function (Digit Span Backwards, Trail-Making, Stroop, Design Fluency). They also completed two behavioral tests of emotion perception (1) an emotion labeling task that measured the ability to identify specific emotions (e.g. sad, happy) of characters in films and (2) an emotion tracking task that measures the ability to continuously track the emotional valence (i.e. negative, neutral, positive) of a character in a film. Lower semantic word knowledge was associated with less accurate emotion labeling (but was not associated with emotion tracking). In contrast, lower executive function was associated with lower accuracy in both labeling and tracking. Effects were robust even after accounting for diagnosis, age, sex, global cognition, and dementia severity. Findings reveal how distinct cognitive processes are linked with different aspects of emotion perception in FTD.

Article	Year
Comparative Transcriptional Analyses in the Nucleus Accumbens Identifies RGS2 as a Key Mediator of Depression-Related Behavior. Biological psychiatry\| PubMed ID: 36075764	2022
A bifunctional optical reporter for tracking estrogen response dynamics in neurons. bioRxiv : the preprint server for biology\| PubMed ID: 41427375	2025
Cognitive processes and emotion perception in frontotemporal dementia. Cognition & emotion\| PubMed ID: 41628296	2026

Sae Yokoyama

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