Pixel-Wise Statistical Mapping with Voltage-Sensitive Dye Imaging Reveals Differential Hippocampal Circuit Effects of Bisphenol A and Related Phenolic Analogs
Abstract
Exposure to environmental chemicals such as bisphenol A (BPA) may affect neural circuit function in subtle and spatially distributed ways that are difficult to attribute to a single circuit element. Here, we developed a voltage-sensitive dye (VSD) imaging analysis pipeline for acute male mouse hippocampal slices. This approach measures stimulus-evoked fractional changes in VSD fluorescence ( Δ F / F 0 ) to generate pixel-wise normalized maps, averages response magnitude within anatomically defined regions of interest (ROIs), and visualizes control-versus-compound differences using pixel-wise statistical maps before and after false discovery rate (FDR) adjustment. We applied this pipeline to compare the acute effects of BPA with those of two structurally related phenolic analogs. Evoked responses were quantified by their peak amplitude and time integral across hippocampal trisynaptic pathways at two stimulation levels determined from input–output relationships, with or without the GAB A A receptor antagonist gabazine (SR-95531; 10 µM). The phenolic analogs reduced circuit responses across multiple ROI-defined conditions, whereas BPA produced comparatively limited effects. These alterations varied with pathway, subfield, age, response metric, and inhibitory state. These findings demonstrate the utility of integrating ROI averages with pixel-wise statistical maps for detecting condition-dependent circuit-level differences between structurally related compounds and indicate that BPA-related phenolic analogs can differ from BPA itself in their acute effects on hippocampal circuitry.
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BibTeX
@article{tominaga2026pixelwise,
title = {{Pixel-Wise Statistical Mapping with Voltage-Sensitive Dye Imaging Reveals Differential Hippocampal Circuit Effects of Bisphenol A and Related Phenolic Analogs}},
author = {Yoko Tominaga and Makiko Taketoshi and Kentaro Tanemura and Takashi Tominaga},
journal = {eneuro},
year = {2026},
month = sep,
doi = {10.1523/eneuro.0165-26.2026},
url = {https://www.eneuro.org/lookup/doi/10.1523/ENEURO.0165-26.2026},
note = {CC BY-NC-SA 4.0},
}
RIS
TY - JOUR
TI - Pixel-Wise Statistical Mapping with Voltage-Sensitive Dye Imaging Reveals Differential Hippocampal Circuit Effects of Bisphenol A and Related Phenolic Analogs
AU - Yoko Tominaga
AU - Makiko Taketoshi
AU - Kentaro Tanemura
AU - Takashi Tominaga
PY - 2026
DA - 2026/09/30
JO - eneuro
DO - 10.1523/eneuro.0165-26.2026
UR - https://www.eneuro.org/lookup/doi/10.1523/ENEURO.0165-26.2026
AB - Exposure to environmental chemicals such as bisphenol A (BPA) may affect neural circuit function in subtle and spatially distributed ways that are difficult to attribute to a single circuit element. Here, we developed a voltage-sensitive dye (VSD) imaging analysis pipeline for acute male mouse hippocampal slices. This approach measures stimulus-evoked fractional changes in VSD fluorescence ( Δ F / F 0 ) to generate pixel-wise normalized maps, averages response magnitude within anatomically defined regions of interest (ROIs), and visualizes control-versus-compound differences using pixel-wise statistical maps before and after false discovery rate (FDR) adjustment. We applied this pipeline to compare the acute effects of BPA with those of two structurally related phenolic analogs. Evoked responses were quantified by their peak amplitude and time integral across hippocampal trisynaptic pathways at two stimulation levels determined from input–output relationships, with or without the GAB A A receptor antagonist gabazine (SR-95531; 10 µM). The phenolic analogs reduced circuit responses across multiple ROI-defined conditions, whereas BPA produced comparatively limited effects. These alterations varied with pathway, subfield, age, response metric, and inhibitory state. These findings demonstrate the utility of integrating ROI averages with pixel-wise statistical maps for detecting condition-dependent circuit-level differences between structurally related compounds and indicate that BPA-related phenolic analogs can differ from BPA itself in their acute effects on hippocampal circuitry.
SN - 2373-2822
ER -