*Result*: Diversity of axon initial segment geometry in the mouse hippocampus and its predicted influence on neuronal excitability.
Title:
Diversity of axon initial segment geometry in the mouse hippocampus and its predicted influence on neuronal excitability.
Authors:
Stevens NA; Institute of Physiology and Pathophysiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Baden-Württemberg, Germany., Achilles M; Institute of Anatomy and Cell Biology, Johannes Kepler University Linz, Krankenhausstrasse 5, 4020 Linz, Upper Austria, Austria.; Clinical Research Institute for Neurosciences, Johannes Kepler University Linz, Wagner-Jauregg-Weg 15, 4020 Linz, Upper Austria, Austria., Monath J; Institute of Anatomy and Cell Biology, Johannes Kepler University Linz, Krankenhausstrasse 5, 4020 Linz, Upper Austria, Austria.; Clinical Research Institute for Neurosciences, Johannes Kepler University Linz, Wagner-Jauregg-Weg 15, 4020 Linz, Upper Austria, Austria., Langer R; Clinical Research Institute for Neurosciences, Johannes Kepler University Linz, Wagner-Jauregg-Weg 15, 4020 Linz, Upper Austria, Austria.; Department of Pathology and Molecular Pathology, Kepler University Hospital Linz, Krankenhausstrasse 5, 4020 Linz, Upper Austria, Austria., Engelhardt M; Institute of Anatomy and Cell Biology, Johannes Kepler University Linz, Krankenhausstrasse 5, 4020 Linz, Upper Austria, Austria.; Clinical Research Institute for Neurosciences, Johannes Kepler University Linz, Wagner-Jauregg-Weg 15, 4020 Linz, Upper Austria, Austria., Both M; Institute of Physiology and Pathophysiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Baden-Württemberg, Germany., Thome C; Institute of Physiology and Pathophysiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Baden-Württemberg, Germany.; Institute of Anatomy and Cell Biology, Johannes Kepler University Linz, Krankenhausstrasse 5, 4020 Linz, Upper Austria, Austria.; Clinical Research Institute for Neurosciences, Johannes Kepler University Linz, Wagner-Jauregg-Weg 15, 4020 Linz, Upper Austria, Austria.
Source:
Cerebral cortex (New York, N.Y. : 1991) [Cereb Cortex] 2025 Nov 27; Vol. 35 (12).
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Oxford University Press Country of Publication: United States NLM ID: 9110718 Publication Model: Print Cited Medium: Internet ISSN: 1460-2199 (Electronic) Linking ISSN: 10473211 NLM ISO Abbreviation: Cereb Cortex Subsets: MEDLINE
Imprint Name(s):
Original Publication: New York, NY : Oxford University Press, c1991-
MeSH Terms:
Hippocampus*/cytology , Hippocampus*/physiology , Axon Initial Segment*/physiology , Axon Initial Segment*/ultrastructure , Pyramidal Cells*/physiology , Pyramidal Cells*/cytology , Axons*/physiology, Action Potentials/physiology ; Dendrites/physiology ; Animals ; Male ; Female ; Mice ; Mice, Inbred C57BL ; Humans
References:
Nat Neurosci. 2009 Aug;12(8):996-1002. (PMID: 19633666)
Neuron. 2010 Jan 14;65(1):7-19. (PMID: 20152109)
Neuron. 2014 Sep 17;83(6):1418-30. (PMID: 25199704)
Neuroscience. 1989;31(3):571-91. (PMID: 2687721)
Front Cell Neurosci. 2020 Jan 22;13:570. (PMID: 32038171)
Brain Res Rev. 2007 Nov;56(1):1-26. (PMID: 17559940)
Brain Res. 1971 Nov;34(1):171-5. (PMID: 5124915)
Proc Natl Acad Sci U S A. 2016 Dec 20;113(51):14841-14846. (PMID: 27930291)
Elife. 2020 Mar 30;9:. (PMID: 32223890)
J Neurophysiol. 2007 May;97(5):3460-72. (PMID: 17314237)
Science. 2015 Nov 27;350(6264):aac9462. (PMID: 26612957)
Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11794-9. (PMID: 19561297)
Sci Adv. 2018 Nov 28;4(11):eaau8621. (PMID: 30498783)
Nature. 2010 Jun 24;465(7301):1070-4. (PMID: 20543823)
Elife. 2025 Feb 03;12:. (PMID: 39898808)
Brain Res. 2001 May 4;900(1):65-71. (PMID: 11325347)
PLoS One. 2021 Nov 19;16(11):e0259918. (PMID: 34797870)
J Neurosci. 2006 Feb 8;26(6):1854-63. (PMID: 16467534)
Brain Res. 1989 May 22;487(2):368-72. (PMID: 2731049)
J Physiol. 2010 Jun 1;588(Pt 11):1829-40. (PMID: 20375142)
J Comput Neurosci. 2022 Aug;50(3):331-355. (PMID: 35653072)
Cereb Cortex. 2024 May 2;34(5):. (PMID: 38745556)
Science. 2022 Sep 23;377(6613):1448-1452. (PMID: 36137045)
Nat Commun. 2021 Jan 4;12(1):23. (PMID: 33397944)
Front Psychiatry. 2014 Aug 21;5:109. (PMID: 25191280)
Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10825-30. (PMID: 12149439)
Nat Neurosci. 2013 Dec;16(12):1812-20. (PMID: 24185428)
J Neurosci. 2010 May 19;30(20):6891-902. (PMID: 20484631)
Brain Commun. 2022 Nov 04;4(6):fcac284. (PMID: 36451656)
Curr Opin Neurobiol. 2018 Aug;51:52-59. (PMID: 29533849)
Hippocampus. 2016 Mar;26(3):341-61. (PMID: 26333017)
Eur J Neurosci. 2011 Nov;34(10):1609-19. (PMID: 22103418)
Cell Rep. 2020 Aug 11;32(6):107988. (PMID: 32783927)
Front Neuroinform. 2009 Jan 28;3:1. (PMID: 19198661)
Acta Pharmacol Sin. 2016 Jan;37(1):75-81. (PMID: 26687934)
J Physiol. 2012 Nov 15;590(22):5571-9. (PMID: 23027822)
J Neurosci. 2010 Feb 3;30(5):1777-87. (PMID: 20130187)
J Neurophysiol. 2008 Oct;100(4):2361-80. (PMID: 18650312)
J Neurosci. 2009 Nov 18;29(46):14472-83. (PMID: 19923281)
Cereb Cortex. 2020 Mar 21;30(2):730-752. (PMID: 31268532)
J Neurosci. 2024 Feb 14;44(7):. (PMID: 38123997)
Elife. 2022 Apr 20;11:. (PMID: 35441590)
Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4051-6. (PMID: 23341597)
Science. 2008 Jul 4;321(5885):140-3. (PMID: 18599792)
eNeuro. 2016 Feb 13;3(1):. (PMID: 27022619)
Nat Neurosci. 2008 Feb;11(2):178-86. (PMID: 18204443)
J Alzheimers Dis. 2020;74(4):1069-1083. (PMID: 32144984)
Neuroscience. 2018 Jan 1;368:268-282. (PMID: 28739523)
Behav Neurosci. 1999 Dec;113(6):1189-203. (PMID: 10636298)
Sci Rep. 2016 Dec 06;6:38242. (PMID: 27922053)
Front Cell Neurosci. 2017 Nov 06;11:332. (PMID: 29170630)
J Neurosci. 2003 Mar 15;23(6):2306-13. (PMID: 12657689)
Cell Rep. 2024 Apr 23;43(4):114100. (PMID: 38607921)
Cells. 2021 Aug 17;10(8):. (PMID: 34440880)
J Neurosci. 1994 Dec;14(12):7347-56. (PMID: 7996180)
J Biol Chem. 2012 May 18;287(21):17656-17661. (PMID: 22511771)
Neurosci Biobehav Rev. 2004 May;28(3):273-83. (PMID: 15225971)
Cell. 2020 Nov 12;183(4):935-953.e19. (PMID: 33186530)
Proc Natl Acad Sci U S A. 2021 Aug 17;118(33):. (PMID: 34389672)
Cells. 2023 Apr 21;12(8):. (PMID: 37190119)
J Neurosci. 2013 Jul 3;33(27):11100-15. (PMID: 23825415)
J Neurosci. 2019 Sep 25;39(39):7790-7800. (PMID: 31399533)
Brain Struct Funct. 2015 Sep;220(5):2873-93. (PMID: 25012113)
Ann N Y Acad Sci. 2018 May;1420(1):46-61. (PMID: 29749636)
Int J Biomed Comput. 1984 Jan-Feb;15(1):69-76. (PMID: 6698635)
Front Neuroanat. 2014 Mar 11;8:11. (PMID: 24653680)
Nature. 2010 Jun 24;465(7301):1075-8. (PMID: 20543825)
Neuron. 2025 Mar 05;113(5):649-669. (PMID: 39947181)
Sci Rep. 2020 Jan 28;10(1):1280. (PMID: 31992746)
J Neurophysiol. 2013 Apr;109(7):1940-53. (PMID: 23324324)
Neuron. 2008 Dec 26;60(6):1010-21. (PMID: 19109908)
Immunol Ser. 1989;45:121-48. (PMID: 2577315)
J Cell Biol. 2025 Jan 6;224(1):. (PMID: 39495320)
Hippocampus. 1998;8(6):608-19. (PMID: 9882018)
J Physiol. 2005 Nov 15;569(Pt 1):41-57. (PMID: 16141270)
J Neurosci. 2019 Jun 26;39(26):5044-5063. (PMID: 31028116)
Hippocampus. 2010 Mar;20(3):423-46. (PMID: 19489002)
Nat Rev Neurosci. 2014 Oct;15(10):655-69. (PMID: 25234264)
Neurochem Int. 2022 Feb;153:105273. (PMID: 34971749)
Neuron. 2000 Oct;28(1):41-51. (PMID: 11086982)
Can J Neurol Sci. 1977 Nov;4(4):273-8. (PMID: 597802)
J Physiol. 2012 Nov 15;590(22):5707-22. (PMID: 22988138)
Nat Methods. 2021 Apr;18(4):374-377. (PMID: 33795878)
Nat Genet. 2008 Sep;40(9):1056-8. (PMID: 18711365)
PLoS Biol. 2009 Apr 21;7(4):e1000089. (PMID: 19385719)
Neuron. 2010 Jan 14;65(1):7-19. (PMID: 20152109)
Neuron. 2014 Sep 17;83(6):1418-30. (PMID: 25199704)
Neuroscience. 1989;31(3):571-91. (PMID: 2687721)
Front Cell Neurosci. 2020 Jan 22;13:570. (PMID: 32038171)
Brain Res Rev. 2007 Nov;56(1):1-26. (PMID: 17559940)
Brain Res. 1971 Nov;34(1):171-5. (PMID: 5124915)
Proc Natl Acad Sci U S A. 2016 Dec 20;113(51):14841-14846. (PMID: 27930291)
Elife. 2020 Mar 30;9:. (PMID: 32223890)
J Neurophysiol. 2007 May;97(5):3460-72. (PMID: 17314237)
Science. 2015 Nov 27;350(6264):aac9462. (PMID: 26612957)
Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11794-9. (PMID: 19561297)
Sci Adv. 2018 Nov 28;4(11):eaau8621. (PMID: 30498783)
Nature. 2010 Jun 24;465(7301):1070-4. (PMID: 20543823)
Elife. 2025 Feb 03;12:. (PMID: 39898808)
Brain Res. 2001 May 4;900(1):65-71. (PMID: 11325347)
PLoS One. 2021 Nov 19;16(11):e0259918. (PMID: 34797870)
J Neurosci. 2006 Feb 8;26(6):1854-63. (PMID: 16467534)
Brain Res. 1989 May 22;487(2):368-72. (PMID: 2731049)
J Physiol. 2010 Jun 1;588(Pt 11):1829-40. (PMID: 20375142)
J Comput Neurosci. 2022 Aug;50(3):331-355. (PMID: 35653072)
Cereb Cortex. 2024 May 2;34(5):. (PMID: 38745556)
Science. 2022 Sep 23;377(6613):1448-1452. (PMID: 36137045)
Nat Commun. 2021 Jan 4;12(1):23. (PMID: 33397944)
Front Psychiatry. 2014 Aug 21;5:109. (PMID: 25191280)
Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10825-30. (PMID: 12149439)
Nat Neurosci. 2013 Dec;16(12):1812-20. (PMID: 24185428)
J Neurosci. 2010 May 19;30(20):6891-902. (PMID: 20484631)
Brain Commun. 2022 Nov 04;4(6):fcac284. (PMID: 36451656)
Curr Opin Neurobiol. 2018 Aug;51:52-59. (PMID: 29533849)
Hippocampus. 2016 Mar;26(3):341-61. (PMID: 26333017)
Eur J Neurosci. 2011 Nov;34(10):1609-19. (PMID: 22103418)
Cell Rep. 2020 Aug 11;32(6):107988. (PMID: 32783927)
Front Neuroinform. 2009 Jan 28;3:1. (PMID: 19198661)
Acta Pharmacol Sin. 2016 Jan;37(1):75-81. (PMID: 26687934)
J Physiol. 2012 Nov 15;590(22):5571-9. (PMID: 23027822)
J Neurosci. 2010 Feb 3;30(5):1777-87. (PMID: 20130187)
J Neurophysiol. 2008 Oct;100(4):2361-80. (PMID: 18650312)
J Neurosci. 2009 Nov 18;29(46):14472-83. (PMID: 19923281)
Cereb Cortex. 2020 Mar 21;30(2):730-752. (PMID: 31268532)
J Neurosci. 2024 Feb 14;44(7):. (PMID: 38123997)
Elife. 2022 Apr 20;11:. (PMID: 35441590)
Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4051-6. (PMID: 23341597)
Science. 2008 Jul 4;321(5885):140-3. (PMID: 18599792)
eNeuro. 2016 Feb 13;3(1):. (PMID: 27022619)
Nat Neurosci. 2008 Feb;11(2):178-86. (PMID: 18204443)
J Alzheimers Dis. 2020;74(4):1069-1083. (PMID: 32144984)
Neuroscience. 2018 Jan 1;368:268-282. (PMID: 28739523)
Behav Neurosci. 1999 Dec;113(6):1189-203. (PMID: 10636298)
Sci Rep. 2016 Dec 06;6:38242. (PMID: 27922053)
Front Cell Neurosci. 2017 Nov 06;11:332. (PMID: 29170630)
J Neurosci. 2003 Mar 15;23(6):2306-13. (PMID: 12657689)
Cell Rep. 2024 Apr 23;43(4):114100. (PMID: 38607921)
Cells. 2021 Aug 17;10(8):. (PMID: 34440880)
J Neurosci. 1994 Dec;14(12):7347-56. (PMID: 7996180)
J Biol Chem. 2012 May 18;287(21):17656-17661. (PMID: 22511771)
Neurosci Biobehav Rev. 2004 May;28(3):273-83. (PMID: 15225971)
Cell. 2020 Nov 12;183(4):935-953.e19. (PMID: 33186530)
Proc Natl Acad Sci U S A. 2021 Aug 17;118(33):. (PMID: 34389672)
Cells. 2023 Apr 21;12(8):. (PMID: 37190119)
J Neurosci. 2013 Jul 3;33(27):11100-15. (PMID: 23825415)
J Neurosci. 2019 Sep 25;39(39):7790-7800. (PMID: 31399533)
Brain Struct Funct. 2015 Sep;220(5):2873-93. (PMID: 25012113)
Ann N Y Acad Sci. 2018 May;1420(1):46-61. (PMID: 29749636)
Int J Biomed Comput. 1984 Jan-Feb;15(1):69-76. (PMID: 6698635)
Front Neuroanat. 2014 Mar 11;8:11. (PMID: 24653680)
Nature. 2010 Jun 24;465(7301):1075-8. (PMID: 20543825)
Neuron. 2025 Mar 05;113(5):649-669. (PMID: 39947181)
Sci Rep. 2020 Jan 28;10(1):1280. (PMID: 31992746)
J Neurophysiol. 2013 Apr;109(7):1940-53. (PMID: 23324324)
Neuron. 2008 Dec 26;60(6):1010-21. (PMID: 19109908)
Immunol Ser. 1989;45:121-48. (PMID: 2577315)
J Cell Biol. 2025 Jan 6;224(1):. (PMID: 39495320)
Hippocampus. 1998;8(6):608-19. (PMID: 9882018)
J Physiol. 2005 Nov 15;569(Pt 1):41-57. (PMID: 16141270)
J Neurosci. 2019 Jun 26;39(26):5044-5063. (PMID: 31028116)
Hippocampus. 2010 Mar;20(3):423-46. (PMID: 19489002)
Nat Rev Neurosci. 2014 Oct;15(10):655-69. (PMID: 25234264)
Neurochem Int. 2022 Feb;153:105273. (PMID: 34971749)
Neuron. 2000 Oct;28(1):41-51. (PMID: 11086982)
Can J Neurol Sci. 1977 Nov;4(4):273-8. (PMID: 597802)
J Physiol. 2012 Nov 15;590(22):5707-22. (PMID: 22988138)
Nat Methods. 2021 Apr;18(4):374-377. (PMID: 33795878)
Nat Genet. 2008 Sep;40(9):1056-8. (PMID: 18711365)
PLoS Biol. 2009 Apr 21;7(4):e1000089. (PMID: 19385719)
Grant Information:
DFG BO 3512/2-1 Deutsche Forschungsgemeinschaft; DFG EN 1240/2-1 Deutsche Forschungsgemeinschaft; PN 458054460 Walter Benjamin Program
Contributed Indexing:
Keywords: Hippocampus; axon initial segment; axon-carrying dendrite; cell morphology; pyramidal neuron
Entry Date(s):
Date Created: 20251209 Date Completed: 20251209 Latest Revision: 20251212
Update Code:
20260130
PubMed Central ID:
PMC12687872
DOI:
10.1093/cercor/bhaf297
PMID:
41364662
Database:
MEDLINE
*Further Information*
*Action potentials, the primary information units of the nervous system, are usually generated at the axon initial segment. Changes in the length and position of the axon initial segment are associated with alterations in neuronal excitability, but there is only limited information about the baseline structural variability of this compartment. This work provides a comprehensive analysis of the diversity of proximal cell geometries across all anatomical axes of the murine hippocampus, encompassing dorsal-ventral, superficial-deep, and proximal-distal regions. We analyzed the morphology of 3,681 hippocampal pyramidal neurons in 12 animals of both sexes, focusing on axon initial segment length, position, and association with proximal cellular features such as the soma and apical dendrite. Notably, neurons with axon-carrying dendrites were significantly more common in ventral compared to dorsal hippocampal areas, which we also found in two of three human samples. We employed NEURON simulations to assess the functional implications of this variability. Here, variation in proximal geometry contributed only minimally to neuronal homeostasis, but instead increased heterogeneity of response patterns across neurons.
(© The Author(s) 2025. Published by Oxford University Press.)*