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Bidirectional control of vesicular GABA release, LTP, and amotivation by GluN2D-selective allosteric modulators and ketamine.

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Paper

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The authors' code

Python · 164 lines · 3.9 KB · no license

  1. #%%
  2. import nd2
  3. import numpy as np
  4. from matplotlib import pyplot as plt
  5. from math import sqrt
  6. from skimage.feature import blob_dog
  7. from skimage.color import rgb2gray
  8. from tifffile import imread
  9. import glob
  12. global soma_size
  13. global soma_radius
  14. global threshold1
  15. global overlap1
  16. global max_sigma1
  17. global min_sigma1
  18. global focalplanepercells
  19. global v
  20. global cells_red
  21. global cells_green
  22. global twentieth_percentile_green
  23. global twentieth_percentile_blue
  24. global twentieth_percentile_red
  26. threshold1 = 0.025
  27. overlap1 = 0.2
  28. soma_size = 14
  29. soma_radius = 1
  30. max_sigma1 = 30
  31. min_sigma1 = 4
  32. focalplanepercells = 5
  33. dapichannel = 2
  34. gfpchannel = 0
  35. bassonchannel = 1
  38. def open_nd2(arg1):
  40. global ndarr
  41. global shape
  42. global soma_radius
  43. global pixelsize
  46. #f = nd2.ND2File('3.0013_#7_CA2_TZ_60X_zstack_1.nd2')
  47. f = nd2.ND2File(arg1)
  48. #print(f.metadata)
  49. metadata = f.metadata
  51. ndarr = f.asarray()
  53. shape = f.shape
  54. pixelsize = f.voxel_size()[1]
  57. ########################################################################
  58. soma_size = 14 #um !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
  59. soma_size_pixels = int(soma_size/pixelsize)
  60. soma_radius = soma_size_pixels/2
  61. #print("opeeeen")
  62. #return ndarr, shape, soma_radius
  64. #ndarr, shape, soma_radius = open_nd2()
  66. #%%
  67. open_nd2("D:\\Rowanlab\\tdTOM_SEP\\FinalRound\\SEP270R\\sl1_topOML_botSLM.nd2")
  69. #%%
  71. def array_to_image(array: np.ndarray, output_path: str = "output.png", cmap: str = "gray") -> None:
  72. """Convert a numpy pixel intensity array to an image using matplotlib."""
  73. plt.imshow(array, vmin=array.min(), vmax=array.max()/4)
  74. plt.imshow(array)
  75. #plt.savefig('my_figureSEP.jpg', dpi=600)
  76. # %%
  78. ndarr2 = ndarr.mean(axis=0).astype(ndarr.dtype)
  79. array_to_image(ndarr2[1,:,:])
  81. red = ndarr2[0,:,:]
  82. green = ndarr2[1,:,:]
  84. # %%
  87. import numpy as np
  88. from scipy.optimize import minimize_scalar
  90. def match_intensity(reference: np.ndarray, target: np.ndarray) -> np.ndarray:
  91. """Scale target image intensity to best match the reference image."""
  92. global result
  93. def mse(scale):
  94. return np.mean((reference - target * scale) ** 2)
  96. result = minimize_scalar(mse, bounds=(-20, 20), method="bounded")
  97. return np.clip(target * result.x, 0, 255).astype(reference.dtype)
  99. matched = match_intensity(green, red)
  101. new_green = green - red*result.x
  102. new_green[new_green < 0] = 0
  103. array_to_image(new_green)
  107. # %%
  108. import numpy as np
  109. import tifffile
  111. def save_12bit_green(array: np.ndarray, output_path: str = "270sl1_CA1_topRAD.tif") -> None:
  112. """Save a 12-bit intensity numpy array as a green RGB 16-bit TIFF."""
  113. assert array.max() <= 4095, "Values exceed 12-bit range (0-4095)"
  114. rgb = np.zeros((*array.shape, 3), dtype=np.uint16)
  115. rgb[..., 1] = array # green channel only
  116. tifffile.imwrite(output_path, rgb)
  118. save_12bit_green(new_green)
  122. # %%
  124. from skimage.feature import blob_dog
  126. blobs_dog = blob_dog(new_green, min_sigma=4, max_sigma=10, threshold=5, overlap=0)
  127. blobs_dog.shape
  130. # %%
  131. import numpy as np
  132. import matplotlib.pyplot as plt
  134. def plot_xy(array: np.ndarray) -> None:
  135. """Plot x, y coordinates from the first two dimensions of a 3D array."""
  136. x = array[:, 1]
  137. y = array[:, 0]
  138. plt.scatter(x.ravel(), y.ravel(), s=1)
  139. plt.xlabel("X")
  140. plt.ylabel("Y")
  141. plt.gca().set_aspect("equal")
  142. plt.show()
  144. plot_xy(blobs_dog)
  147. # %%
  149. def density(array: np.ndarray) -> None:
  150. """Plot x, y coordinates from the first two dimensions of a 3D array."""
  152. counter = 0
  153. limit = 1500
  154. for item in array:
  155. if item[0] > limit:
  156. counter += 1
  157. print(counter/(limit*0.03*2304*0.03))
  158. print(counter/((2304-limit)*0.03*2304*0.03))
  160. density(blobs_dog)
  164. # %%

SEP summarizer.py at commit a8262a6, no license · at the source

Overview

Authors: Viktor J. Oláh1,2, Isabelle F. Witteveen3,2, Tue G. Banke3,2, Alexa M. Leahy4, Ryan Keable5, Riley E. Perszyk3, Cara T. Khayat3, TrangKimberly T. Nguyen3, Brianna J. Bixler1, Frances G. Ghinger1, Detlef Vullhorst6,7, Yeeun Yook1, Scott J. Myers3, Elijah Z. Ullman3, Jing Zhang3, Hao Xing3, John F. Traynelis3, Eva S. Diaz3, Sukhan Kim3, Sophia Boraschi3
and 15 other authorsNicholas S. Akins8, Ken H. Liu8, Alet van der Westhuyzen8, Yanli Yang8, Chad R. Camp3, Andres Buonanno6, Randy A. Hall3, James Q. Zheng1, Dennis C. Liotta8, Matthew J. Kennedy5, Katherine W. Roche6, Shannon L. Gourley4, Hongjie Yuan3, Matthew J.M. Rowan1,9,10,11, Stephen F. Traynelis3,9,10,12
ORCID iDs: Stephen F. Traynelis
  1. Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA
  2. Senior author
  3. Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA
  4. Department of Pediatrics, Emory University School of Medicine, Atlanta GA 30322, USA
  5. Department of Pharmacology, University of Colorado-Denver, Aurora CO 80045, USA
  6. National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA
  7. National Institute of Child Health and Human Development, Bethesda, MD 20892, USA
  8. Department of Chemistry, Emory University, Atlanta GA 30322, USA
  9. Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA
  10. These authors contributed equally
  11. Present address: Department of Cellular and Molecular Medicine, Florida International University, Miami, FL 33199, USA
  12. Lead contact
Institutions: Emory University (United States); University of Colorado Denver (United States); National Institute of Neurological Disorders and Stroke (United States)
Journal: Cell reports, volume 45, issue 8, article 117707
Dates: published online 24 July 2026; in print July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.celrep.2026.117707 · PMID 42501328 · PMCID PMC13581442 · OpenAlex W7170740590
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: depression (population), cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics, Machine learning, Evoked potentials
Keywords: Depression, NMDAR, ketamine, Interneuron, Presynaptic, Glun2d, Cp: Neuroscience
Topic: Neuroscience and Neuropharmacology Research (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: NIH HHS (P51 OD011132, S10 OD028673); NICHD NIH HHS (R01 HD082373); NINDS NIH HHS (R21 NS133960, R35 NS111619, R21 NS132393, R35 NS116879, T32 NS096050); NIMH NIH HHS (R37 MH117103, R01 MH117103, R01 MH133798); NIA NIH HHS (RF1 AG079269, R01 AG079269); National Institute on Aging; National Institute of Neurological Disorders and Stroke; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Mental Health
Citations: not cited yet (Europe PMC); 94 references in the paper
Research resources: goat anti-chicken Alexa Fluor 488 RRID:AB_2534096, goat anti-rabbit Alexa Fluor 647 RRID:AB_2722623, Goat anti-guinea pig Alexa Fluor 647 RRID:AB_2827756, Guinea pig anti-parvalbumin RRID:AB_2927389, Chicken anti-GFP RRID:AB_300798, Rabbit anti-GFP RRID:AB_303395, Mouse anti- α-tubulin RRID:AB_477583, Rabbit anti-Bassoon RRID:AB_887697, guinea pig polyclonal anti-VGLUT1 RRID:AB_887878, Mouse: C57Bl6 RRID:IMSR_JAX:000664, Mouse: B6.129P2-Pvalbtm1(cre)Arbr/J RRID:IMSR_JAX:017320, RRID:SCR_012499

Abstract

GABAergic inhibitory interneurons balance brain activity by suppressing excessive excitatory signaling and shaping network oscillations. Despite this critical function, our understanding of how neural circuits regulate GABAergic systems remains limited. Although N-methyl-D-aspartate receptor (NMDAR) functionality is defined by the GluN2A-D subunits, the interneuron NMDAR subunit composition remains unknown. Here, we show that GluN2D-NMDARs reside at presynaptic terminals of hippocampal parvalbumin-interneurons, and that the GluN2D intracellular C-terminal contains presynaptic targeting information. GluN2D-NMDARs are activated by changes in basal glutamate to bidirectionally control GABA release. Importantly, inhibition of GABA release by GluN2C/D modulators and subanesthetic ketamine is absent in mice lacking GluN2D in parvalbumin-interneurons, suggesting that GluN2D-dependent presynaptic regulation of GABA release may underlie some of ketamine’s effects. The GluN2C/D-selective inhibitor NAB14 recapitulates durable ketamine-induced enhancement of long-term potentiation (LTP) and recovery of reward motivation in a behavioral model of depression without ketamine’s undesirable effects, suggesting that GluN2D-NMDARs could be a therapeutically relevant target.

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

Repository

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

microcircuitprojects/presynaptic_glun2d

License: none: the authors keep all their rights
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: a8262a6cebe215ce6a8b9f5415f2fb65322d9f9a, 21 May 2026
Languages: Python (3)
Size: 3 files, 3 scripts
Software Heritage: not archived
Found in: “Data and code availability”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: Matplotlib (3 files), NumPy (3 files), scikit-image (3 files), tifffile (2 files), SciPy (1 file)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
3 files
At the source: github.com/MicrocircuitProjects/Presynaptic_GluN2D/releases/tag/Puncta_finder

The paper's code and data availability statement is in the Data section.

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;
  • 3 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 and code availability

Data: Data reported in this paper will be shared by the lead contact upon request.

Code: Code is available from GitHub at the following link https://github.com/MicrocircuitProjects/Presynaptic_GluN2D/releases/tag/Puncta_finder

Other Items: Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request. All materials used are commercially available from indicated vendors; compounds synthesized (NAB-14, (S)-EU997–74) are commercially available from multiple vendors, and the synthetic methods are published. Software is commercially available from the indicated vendors.

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 2, 28 September 2026

  • Publisher: n/a → Cell Press
  • Authors: added Stephen F. Traynelis (0000-0002-3750-9615); removed Stephen F. Traynelis

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 35 authors, 7 keywords, 9 funders, 94 references, 12 RRIDs.

Cite

This paper

Oláh, V. J., Witteveen, I. F., Banke, T. G., Leahy, A. M., Keable, R., Perszyk, R. E., Khayat, C. T., Nguyen, T. T., Bixler, B. J., Ghinger, F. G., Vullhorst, D., Yook, Y., Myers, S. J., Ullman, E. Z., Zhang, J., Xing, H., Traynelis, J. F., Diaz, E. S., Kim, S., . . . Traynelis, S. F. (2026). Bidirectional control of vesicular GABA release, LTP, and amotivation by GluN2D-selective allosteric modulators and ketamine. Cell reports, 45(8), 117707. https://doi.org/10.1016/j.celrep.2026.117707

BibTeX

@article{olah2026bidirectional,
author = {Oláh, Viktor J. and Witteveen, Isabelle F. and Banke, Tue G. and Leahy, Alexa M. and Keable, Ryan and Perszyk, Riley E. and Khayat, Cara T. and Nguyen, TrangKimberly T. and Bixler, Brianna J. and Ghinger, Frances G. and Vullhorst, Detlef and Yook, Yeeun and Myers, Scott J. and Ullman, Elijah Z. and Zhang, Jing and Xing, Hao and Traynelis, John F. and Diaz, Eva S. and Kim, Sukhan and Boraschi, Sophia and Akins, Nicholas S. and Liu, Ken H. and van der Westhuyzen, Alet and Yang, Yanli and Camp, Chad R. and Buonanno, Andres and Hall, Randy A. and Zheng, James Q. and Liotta, Dennis C. and Kennedy, Matthew J. and Roche, Katherine W. and Gourley, Shannon L. and Yuan, Hongjie and Rowan, Matthew J.M. and Traynelis, Stephen F.},
title = {{Bidirectional control of vesicular GABA release, LTP, and amotivation by GluN2D-selective allosteric modulators and ketamine}},
journal = {Cell reports},
year = {2026},
month = jul,
volume = {45},
number = {8},
pages = {117707},
publisher = {Cell Press},
issn = {2211-1247},
doi = {10.1016/j.celrep.2026.117707},
url = {https://doi.org/10.1016/j.celrep.2026.117707},
pmid = {42501328},
pmcid = {PMC13581442}
}

RIS

TY - JOUR
AU - Oláh, Viktor J.
AU - Witteveen, Isabelle F.
AU - Banke, Tue G.
AU - Leahy, Alexa M.
AU - Keable, Ryan
AU - Perszyk, Riley E.
AU - Khayat, Cara T.
AU - Nguyen, TrangKimberly T.
AU - Bixler, Brianna J.
AU - Ghinger, Frances G.
AU - Vullhorst, Detlef
AU - Yook, Yeeun
AU - Myers, Scott J.
AU - Ullman, Elijah Z.
AU - Zhang, Jing
AU - Xing, Hao
AU - Traynelis, John F.
AU - Diaz, Eva S.
AU - Kim, Sukhan
AU - Boraschi, Sophia
AU - Akins, Nicholas S.
AU - Liu, Ken H.
AU - van der Westhuyzen, Alet
AU - Yang, Yanli
AU - Camp, Chad R.
AU - Buonanno, Andres
AU - Hall, Randy A.
AU - Zheng, James Q.
AU - Liotta, Dennis C.
AU - Kennedy, Matthew J.
AU - Roche, Katherine W.
AU - Gourley, Shannon L.
AU - Yuan, Hongjie
AU - Rowan, Matthew J.M.
AU - Traynelis, Stephen F.
TI - Bidirectional control of vesicular GABA release, LTP, and amotivation by GluN2D-selective allosteric modulators and ketamine
T2 - Cell reports
J2 - Cell Rep
PY - 2026
DA - 2026/07/24
VL - 45
IS - 8
SP - 117707
SN - 2211-1247
PB - Cell Press
DO - 10.1016/j.celrep.2026.117707
UR - https://doi.org/10.1016/j.celrep.2026.117707
LA - en
ER -

CSL-JSON

{
"id": "10.1016/j.celrep.2026.117707",
"type": "article-journal",
"title": "Bidirectional control of vesicular GABA release, LTP, and amotivation by GluN2D-selective allosteric modulators and ketamine",
"container-title": "Cell reports",
"author": [
{
"family": "Oláh",
"given": "Viktor J."
},
{
"family": "Witteveen",
"given": "Isabelle F."
},
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},
{
"family": "Leahy",
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},
{
"family": "Keable",
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},
{
"family": "Perszyk",
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},
{
"family": "Khayat",
"given": "Cara T."
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{
"family": "Nguyen",
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{
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{
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},
{
"family": "Xing",
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{
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{
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{
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{
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{
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{
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{
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{
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{
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{
"family": "Zheng",
"given": "James Q."
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{
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{
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{
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{
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"container-title-short": "Cell Rep",
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"PMID": "42501328",
"PMCID": "PMC13581442",
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"language": "en",
"issued": {
"date-parts": [
[
2026,
7,
24
]
]
}
}

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