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Neuronal toll-like receptor-4 regulation of matrix metalloproteinase-9 activity mediates dentate circuit dysfunction after traumatic brain injury.

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Paper

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The authors' code

Python · 307 lines · 13 KB · MIT

  1. #!/usr/bin/env python3
  2. # -*- coding: utf-8 -*-
  3. """
  4. StyleSheets
  6. @author: amandaschott
  7. """
  8. from copy import deepcopy
  10. ##############################################################################
  11. ################ BUTTONS ################
  12. ##############################################################################
  14. TOGGLE_BTN = {'QPushButton' : {
  15. 'background-color' : 'whitesmoke',
  16. 'border-width' : '1px',
  17. 'border-style' : 'solid',
  18. 'border-color' : 'gray',
  19. 'border-radius' : '3px',
  20. 'color' : 'black',
  21. 'font-weight' : 'normal',
  22. 'padding' : '4px',
  23. },
  25. 'QPushButton:pressed' : {
  26. 'background-color' : 'dimgray',
  27. 'border-color' : 'gray',
  28. 'color' : 'white',
  29. },
  31. 'QPushButton:checked' : {
  32. 'background-color' : 'darkgray',
  33. 'border-color' : 'gray',
  34. 'color' : 'black',
  35. },
  37. 'QPushButton:disabled' : {
  38. 'background-color' : 'gainsboro',
  39. 'border-color' : 'darkgray',
  40. 'color' : 'gray',
  41. },
  43. 'QPushButton:disabled:checked' : {
  44. 'background-color' : 'darkgray',
  45. 'border-color' : 'darkgray',
  46. 'color' : 'dimgray',
  47. }
  48. }
  50. ### "sunken" toggle buttons (e.g. on Toothy's home screen)
  52. INSET_BTN = deepcopy(TOGGLE_BTN)
  53. INSET_BTN['QPushButton'].update({
  54. 'border-width' : '2px',
  55. 'border-style' : 'outset',
  56. })
  57. INSET_BTN['QPushButton:pressed']['border-style'] = 'inset'
  58. INSET_BTN['QPushButton:checked']['border-style'] = 'inset'
  59. INSET_BTN['QPushButton:disabled']['border-style'] = 'outset'
  60. INSET_BTN['QPushButton:disabled:checked']['border-style'] = 'inset'
  62. BOLD_INSET_BTN = deepcopy(INSET_BTN)
  63. BOLD_INSET_BTN['QPushButton']['border-width'] = '3px'
  64. BOLD_INSET_BTN['QPushButton']['font-weight'] = 'bold'
  66. HOME_BTN = deepcopy(BOLD_INSET_BTN)
  67. HOME_BTN['QPushButton']['background-color'] = 'gainsboro'
  69. ### expand/collapse buttons for settings panes, plots, etc
  71. EXPAND_LEFT_BTN = deepcopy(INSET_BTN) # frequency plots
  72. EXPAND_LEFT_BTN['QPushButton'].update({
  73. 'image' : 'url(:/icons/double_chevron_left.png)',
  74. 'image-position' : 'left',
  75. })
  76. EXPAND_LEFT_BTN['QPushButton:checked']['image'] = 'url(:/icons/double_chevron_right.png)'
  78. EXPAND_DOWN_BTN = deepcopy(INSET_BTN) # settings pane
  79. EXPAND_DOWN_BTN['QPushButton'].update({
  80. 'image' : 'url(:/icons/double_chevron_down.png)',
  81. 'image-position' : 'right',
  82. })
  83. EXPAND_DOWN_BTN['QPushButton:checked']['image'] = 'url(:/icons/double_chevron_up.png)'
  85. EXPAND_PARAMS_BTN = deepcopy(EXPAND_DOWN_BTN) # parameter inputs
  86. EXPAND_PARAMS_BTN['QPushButton']['icon'] = 'url(:/icons/settings.png)'
  88. EXPAND_AUX_BTN = deepcopy(EXPAND_DOWN_BTN)
  89. EXPAND_AUX_BTN['QPushButton']['icon'] = 'url(:/icons/view.png)'
  91. ### circular colored buttons in the main processed data hub
  93. ANALYSIS_BTN = {'QPushButton' : {
  94. 'background-color' : 'white',
  95. 'border-width' : '4px',
  96. 'border-style' : 'outset',
  97. 'border-color' : 'rgb(128,128,128)',
  98. 'border-radius' : '11px',
  99. 'min-width' : '15px',
  100. 'max-width' : '15px',
  101. 'min-height' : '15px',
  102. 'max-height' : '15px',
  103. },
  105. 'QPushButton:disabled' : {
  106. 'background-color' : 'rgb(220,220,220)',
  107. },
  109. 'QPushButton:pressed' : {
  110. 'background-color' : 'dimgray',
  111. }
  112. }
  114. ### convert between relative and absolute timepoints
  116. TRANGE_TOGGLE_BTN = deepcopy(TOGGLE_BTN)
  117. TRANGE_TOGGLE_BTN['QPushButton'].update({
  118. 'border' : 'none',
  119. "color": "red", # REMOVE KNE
  120. 'outline' : 'none',
  121. #'image' : 'url(:/icons/warning_yellow.png)',
  122. 'image' : 'url(:/icons/swap_arrows_vert.png)',
  123. #'background-image':'url(:/icons/swap_arrows_vert.png)',
  124. 'padding':'1px',
  125. })
  127. ### show/hide raw recording metadata
  128. # can remove
  129. # META_TOGGLE_BTN = deepcopy(TOGGLE_BTN)
  130. # META_TOGGLE_BTN['QPushButton'].update({
  131. # 'image' : 'url(:/icons/info_blue.png)',
  132. # 'padding' : '4px',
  133. # })
  135. ##############################################################################
  136. ################ ICONS ################
  137. ##############################################################################
  139. ICON_BTN = {'QPushButton' : {
  140. 'border' : 'none',
  141. 'outline' : 'none',
  142. 'padding' : '0px',
  143. },
  145. 'QPushButton#params_warning' : {
  146. 'image' : 'url(:/icons/warning_yellow.png)',
  147. },
  148. }
  151. ##############################################################################
  152. ################ INPUT WIDGETS ################
  153. ##############################################################################
  156. ### numeric inputs and dropdown menus
  158. PARAM_INPUTS = {'QAbstractSpinBox' : {
  159. 'background-color':'white',
  160. 'color':'black',
  161. },
  162. 'QAbstractSpinBox:disabled' : {'color':'gainsboro',},
  164. 'QComboBox' : {'color':'black',},
  165. 'QComboBox:open' : {'background-color':'white',
  166. 'color' : 'black',},
  167. }
  169. ### missing/invalid input parameters
  171. PARAM_INPUTS_OFF = deepcopy(PARAM_INPUTS)
  172. PARAM_INPUTS_OFF['QAbstractSpinBox'].update({'background-color' : 'red',
  173. 'color' : 'transparent'})
  174. PARAM_INPUTS_OFF['QAbstractSpinBox:disabled']['color'] = 'transparent'
  176. ### list interfaces
  178. QLIST = {'QListWidget' : {
  179. 'background-color' : 'rgba(255,255,255,50)',
  180. 'border-width' : '2px',
  181. 'border-style' : 'groove',
  182. 'border-color' : 'rgb(150,150,150)',
  183. 'border-radius' : '2px',
  184. 'padding' : '0px',
  185. },
  187. 'QListWidget::item' : {
  188. 'background-color' : 'rgb(255,255,255)',
  189. 'color' : 'black',
  190. 'border-width' : '1px',
  191. 'border-style' : 'solid',
  192. 'border-color' : 'rgb(200,200,200)',
  193. 'border-radius' : '1px',
  194. 'padding' : '4px',
  195. },
  197. 'QListWidget::item:selected' : {
  198. 'background-color' : 'rgba(85,70,160,200)',
  199. 'color' : 'white',
  200. }
  201. }
  203. ### context menu
  205. QMENU = {'QMenu' : {
  206. 'border-width' : '4px',
  207. 'border-style' : 'ridge',
  208. 'border-color' : 'gray',
  209. },
  211. 'QMenu::item' : {
  212. 'padding' : '2px 5px 2px 20px',
  213. },
  215. 'QMenu::item:selected' : {
  216. 'background-color' : 'rgba(85,70,160,200)',
  217. 'color' : 'white',
  218. },
  219. 'QMenu::item:disabled' : {
  220. 'color' : 'lightgray',
  221. },
  223. 'QLabel' : {
  224. 'background-color' : 'rgb(200,200,200)',
  225. 'border-bottom' : '2px solid dimgray',
  226. 'border-top' : '2px solid dimgray',
  227. 'padding' : '2px',
  228. },
  229. 'QLabel#top_header' : {'border-top':'none'},
  230. }
  233. ##############################################################################
  234. ################ CHANNEL SELECTION GUI ################
  235. ##############################################################################
  238. ### centralized tools for event detection/curation
  240. EVENT_GBOX = {'QGroupBox' : {
  241. 'background-color' : 'rgba(220,220,220,100)', # gainsboro
  242. 'border' : '2px solid darkgray',
  243. 'border-top' : '5px double black',
  244. 'border-radius' : '6px',
  245. 'border-top-left-radius' : '1px',
  246. 'border-top-right-radius' : '1px',
  247. 'font-size' : '16pt',
  248. 'font-weight' : 'bold',
  249. 'margin-top' : '10px',
  250. 'padding' : '2px',
  251. 'padding-bottom' : '10px',
  252. },
  254. 'QGroupBox::title' : {
  255. 'background-color' : 'palette(button)',
  256. 'subcontrol-origin' : 'margin',
  257. 'subcontrol-position' : 'top center',
  258. 'padding' : '1px 4px', # top, right, bottom, left
  259. }
  260. }
  262. ### color-coded line (bottom of event boxes)
  264. EVENT_GBOX_LINE = {'QLabel' : {
  265. 'border' : '1px solid transparent',
  266. 'border-bottom-width' : '3px',
  267. 'border-bottom-color' : 'black',
  268. 'max-height' : '2px',
  269. }
  270. }
  272. ### event show/hide button (eye icon)
  274. EVENT_SHOW_BTN = {'QPushButton' : {
  275. 'background-color' : 'whitesmoke',
  276. 'border' : '2px outset gray',
  277. 'image' : 'url(:/icons/show_outline.png)',
  278. },
  280. 'QPushButton:checked' : {
  281. 'background-color' : 'gainsboro',
  282. 'border' : '2px inset gray',
  283. 'image' : 'url(:/icons/hide_outline.png)',
  284. }
  285. }
  288. ##############################################################################
  289. ################ EVENT ANALYSIS GUI ################
  290. ##############################################################################
  293. EVENT_SETTINGS_GBOX = {'QGroupBox' : {
  294. 'border' : '1px solid gray',
  295. 'border-radius' : '8px',
  296. 'font-size' : '16pt',
  297. 'font-weight' : 'bold',
  298. 'margin-top' : '10px',
  299. 'padding' : '10px 5px 10px 5px',
  300. },
  302. 'QGroupBox::title' : {
  303. 'subcontrol-origin' : 'margin',
  304. 'subcontrol-position' : 'top left',
  305. 'padding' : '2px 5px',
  306. }
  307. }

QSS.py at commit 7fb70f4, under MIT · at the source

Overview

Authors: Deepak Subramanian1, Erick M Contreras1, Laura Dovek1, Razieh Jaberi1, Emmanuel Green1, Ysabelle K Lao1, Iryna M Ethell2, Vijayalakshmi Santhakumar1
ORCID iDs: Vijayalakshmi Santhakumar
  1. Department of Molecular, Cell and Systems Biology, University of California Riverside, Riverside, CA 92521 USA
  2. Biomedical Sciences, University of California Riverside, Riverside, CA 92521 USA
Institutions: University of California, Riverside (United States)
Journal: Journal of neuroinflammation, volume 23, issue 1, article 271
Dates: received 9 January 2026; accepted 22 May 2026; published online 3 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s12974-026-03890-4 · PMID 42237180 · PMCID PMC13474604 · OpenAlex W7163396291
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: mouse (organism), rat (organism), traumatic brain injury (population), cellular / molecular (subfield)
Methods: Statistics
Keywords: Traumatic Brain Injury, Dentate gyrus, Toll-like Receptor 4, Matrix Metalloproteinase-9, Neuro-immune signaling, Synaptic plasticity
MeSH: Brain Injuries, Traumatic*, Dentate Gyrus*, Matrix Metalloproteinase 9*, Neurons*, Toll-Like Receptor 4*, Animals, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Rats, Rats, Sprague-Dawley, Signal Transduction (* major topic)
Topic: Traumatic Brain Injury and Neurovascular Disturbances (Neurology, Medicine), according to OpenAlex
Funding: National Institutes of Health (NIH) NINDS (F31NS124290, R01 NS069861,R01NS097750); NINDS NIH HHS (F31 NS124290, F31 NS131052, R01 NS069861, R01 NS097750, R01 NS134914); CDMRP- Epilepsy Research Program ; Idea Development Award (W81XWH-21-1-0684)
Citations: not cited yet (Europe PMC); 88 references in the paper

Abstract

Neuroinflammatory pathways activated by traumatic brain injury (TBI) are critical mediators of long-term neurological dysfunction and represent promising therapeutic targets. Toll-like receptor 4 (TLR4), an innate immune receptor, was previously shown to contribute to increased seizure susceptibility and cognitive deficits in rats after lateral fluid percussion injury (FPI). However, the cellular and molecular mechanisms underlying TLR4-mediated circuit dysfunction early after brain injury are not fully understood. In this study, we define a cell- and circuit- specific neuroimmune-enzyme effector signaling axis that mediates early post-TBI circuit dysfunction in the hippocampal Dentate Gyrus (DG). Using ex vivo electrophysiology in rat and mouse models one week after brain injury, we demonstrate that neuronal TLR4 signaling regulates both excitatory and inhibitory synaptic inputs to dentate granule cells (DGC). Collectively, pharmacological inhibition of TLR4 in rats and cell-type-specific deletion of TLR4 in mice show that neuronal TLR4 mediates injury-driven increase in DGC excitatory input frequency and relies on downstream activation of Matrix Metalloproteinase-9 (MMP-9). In contrast, TLR4 signaling contributed to a decrease in inhibitory current frequency after injury, but independent of MMP-9, revealing a mechanistic divergence. Systemic inhibition of either TLR4 signaling or MMP-9 activity in rats within 24 h after injury reduced network hyperexcitability and improved long-term potentiation (LTP) in the DG measured in vivo one week after injury. Either TLR4 or MMP-9 inhibition early after injury effectively attenuated spatial memory deficits in a Barnes maze task one month post-injury. Paradoxically, in sham controls, inhibition of TLR4 increased the frequency of both excitatory and inhibitory inputs to DGCs and augmented network excitability, without altering MMP-9 levels, identifying context-dependent roles for TLR4 signaling. Together, these results identify a novel TLR4 -MMP-9 axis as a key driver of early post-TBI dentate gyrus circuit dysfunction and behavioral deficits.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12974-026-03890-4.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repository

Its files are read in the Code ↔ Paper reader above.

Farrell-Laboratory/Toothy

License: MIT
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: 7fb70f400ae3bbc2be65f5030aa7429db6d93560, 9 June 2026
Languages: Python (21)
Size: 73 files, 21 scripts
Software Heritage: not archived
Found in: the text, “In vivo electrophysiology”
Holds: README, license file, environment (environment.yml, pyproject.toml)
Not found: CITATION.cff, tests, continuous integration, documentation
Tools: NumPy (11 files), pandas (8 files), Matplotlib (6 files), SciPy (6 files), h5py (4 files), seaborn (4 files), SpikeInterface (4 files), Neo (2 files), Open Ephys analysis tools (1 file), scikit-learn (1 file)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
23 files
At the source: github.com/Farrell-Laboratory/Toothy

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 21 scripts, each with its path and the digest of its content;
  • no match between paragraphs and code yet;
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data availability

All data are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 6 keywords, 13 MeSH terms, 3 funders, 87 references.

Cite

This paper

Subramanian, D., Contreras, E. M., Dovek, L., Jaberi, R., Green, E., Lao, Y. K., Ethell, I. M., & Santhakumar, V. (2026). Neuronal toll-like receptor-4 regulation of matrix metalloproteinase-9 activity mediates dentate circuit dysfunction after traumatic brain injury. Journal of neuroinflammation, 23(1), 271. https://doi.org/10.1186/s12974-026-03890-4

BibTeX

@article{subramanian2026neuronal,
author = {Subramanian, Deepak and Contreras, Erick M and Dovek, Laura and Jaberi, Razieh and Green, Emmanuel and Lao, Ysabelle K and Ethell, Iryna M and Santhakumar, Vijayalakshmi},
title = {{Neuronal toll-like receptor-4 regulation of matrix metalloproteinase-9 activity mediates dentate circuit dysfunction after traumatic brain injury}},
journal = {Journal of neuroinflammation},
year = {2026},
month = jun,
volume = {23},
number = {1},
pages = {271},
publisher = {BMC},
issn = {1742-2094},
doi = {10.1186/s12974-026-03890-4},
url = {https://doi.org/10.1186/s12974-026-03890-4},
pmid = {42237180},
pmcid = {PMC13474604}
}

RIS

TY - JOUR
AU - Subramanian, Deepak
AU - Contreras, Erick M
AU - Dovek, Laura
AU - Jaberi, Razieh
AU - Green, Emmanuel
AU - Lao, Ysabelle K
AU - Ethell, Iryna M
AU - Santhakumar, Vijayalakshmi
TI - Neuronal toll-like receptor-4 regulation of matrix metalloproteinase-9 activity mediates dentate circuit dysfunction after traumatic brain injury
T2 - Journal of neuroinflammation
J2 - J Neuroinflammation
PY - 2026
DA - 2026/06/03
VL - 23
IS - 1
SP - 271
SN - 1742-2094
PB - BMC
DO - 10.1186/s12974-026-03890-4
UR - https://doi.org/10.1186/s12974-026-03890-4
LA - en
ER -

CSL-JSON

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"title": "Neuronal toll-like receptor-4 regulation of matrix metalloproteinase-9 activity mediates dentate circuit dysfunction after traumatic brain injury",
"container-title": "Journal of neuroinflammation",
"author": [
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"family": "Subramanian",
"given": "Deepak"
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{
"family": "Contreras",
"given": "Erick M"
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{
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{
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{
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{
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"given": "Ysabelle K"
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{
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"given": "Iryna M"
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{
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"given": "Vijayalakshmi"
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],
"container-title-short": "J Neuroinflammation",
"volume": "23",
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"DOI": "10.1186/s12974-026-03890-4",
"PMID": "42237180",
"PMCID": "PMC13474604",
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"language": "en",
"issued": {
"date-parts": [
[
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3
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]
}
}

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