Increased intrinsic membrane excitability is associated with hypertrophic olivary degeneration in spinocerebellar ataxia type 1.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
23 Oct 2023
23 Oct 2023
Historique:
pubmed:
14
11
2023
medline:
14
11
2023
entrez:
14
11
2023
Statut:
epublish
Résumé
One of the characteristic areas of brainstem degeneration across multiple spinocerebellar ataxias (SCAs) is the inferior olive (IO), a medullary nucleus that plays a key role in motor learning. In addition to its vulnerability in SCAs, the IO is also susceptible to a distinct pathology known as hypertrophic olivary degeneration (HOD). Clinically, HOD has been exclusively observed after lesions in the brainstem disrupt inhibitory afferents to the IO. Here, for the first time, we describe HOD in another context: spinocerebellar ataxia type 1 (SCA1). Using the genetically-precise SCA1 knock-in mouse model (SCA1-KI; both sexes used), we assessed SCA1-associated changes in IO neuron structure and function. Concurrent with degeneration, we found that SCA1-KI IO neurons are hypertrophic, exhibiting early dendrite lengthening and later somatic expansion. Unlike in previous descriptions of HOD, we observed no clear loss of IO inhibitory innervation; nevertheless, patch-clamp recordings from brainstem slices reveal that SCA1-KI IO neurons are hyperexcitable. Rather than synaptic disinhibition, we identify increases in
Identifiants
pubmed: 37961407
doi: 10.1101/2023.10.23.563657
pmc: PMC10634770
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NINDS NIH HHS
ID : R01 NS085054
Pays : United States
Organisme : NINDS NIH HHS
ID : R37 NS022920
Pays : United States
Déclaration de conflit d'intérêts
Conflicts of Interests The authors declare no competing financial interests.
Références
Nat Biotechnol. 2010 Apr;28(4):348-53
pubmed: 20231818
Acta Neuropathol. 2012 Jul;124(1):1-21
pubmed: 22684686
Neurobiol Dis. 2015 Jan;73:174-88
pubmed: 25301414
PLoS Genet. 2010 Jul 08;6(7):e1001021
pubmed: 20628574
Prog Neurobiol. 2013 May;104:38-66
pubmed: 23438480
J Physiol. 1986 Jul;376:163-82
pubmed: 3795074
Acta Neuropathol. 1981;54(4):275-82
pubmed: 7270084
Neuroscience. 2009 Sep 1;162(3):797-804
pubmed: 19393291
Cerebellum. 2013 Aug;12(4):493-503
pubmed: 23389921
Brain Struct Funct. 2019 May;224(4):1677-1695
pubmed: 30929054
Elife. 2018 Dec 03;7:
pubmed: 30507379
Front Cell Neurosci. 2015 Apr 13;9:122
pubmed: 25918500
Nat Neurosci. 2006 Mar;9(3):389-97
pubmed: 16474392
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Neuron. 2009 May 28;62(4):555-65
pubmed: 19477156
Cell. 1995 Sep 22;82(6):937-48
pubmed: 7553854
Anat Rec (Hoboken). 2014 Feb;297(2):289-300
pubmed: 24443186
JCI Insight. 2018 Nov 2;3(21):
pubmed: 30385727
Adv Neurol. 1984;41:5-12
pubmed: 6496230
Ann Clin Transl Neurol. 2018 Jan 22;5(3):297-314
pubmed: 29560375
Nature. 2007 Jan 11;445(7124):168-76
pubmed: 17151600
Case Rep Neurol. 2017 Nov 10;9(3):267-271
pubmed: 29422848
Front Cell Neurosci. 2013 Apr 23;7:48
pubmed: 23630465
Z Neurol. 1973;205(2):153-74
pubmed: 4127009
Cerebellum. 2017 Feb;16(1):230-252
pubmed: 27193702
Mov Disord. 2021 Mar;36(3):622-631
pubmed: 33151010
Br J Pharmacol. 2011 Nov;164 Suppl 1:S1-324
pubmed: 22040146
J Neurosci. 2013 Feb 20;33(8):3668-78
pubmed: 23426693
Neurology. 1998 Jan;50(1):106-13
pubmed: 9443466
Trends Neurosci. 1998 Sep;21(9):391-400
pubmed: 9735947
Genome Biol. 2014;15(12):550
pubmed: 25516281
J Neurol Sci. 2016 Nov 15;370:180-186
pubmed: 27772756
Nat Commun. 2014 Jul 11;5:4342
pubmed: 25014658
Front Neurol. 2017 Jun 29;8:302
pubmed: 28706504
Neuropathol Appl Neurobiol. 1994 Feb;20(1):38-46
pubmed: 7516051
Clin Anat. 2017 May;30(4):543-549
pubmed: 28247932
Eur J Morphol. 1990;28(2-4):240-55
pubmed: 2245133
Eur J Morphol. 1990;28(2-4):224-39
pubmed: 2245132
Hum Mol Genet. 2013 Jan 15;22(2):271-83
pubmed: 23087021
Nat Protoc. 2014 Jan;9(1):193-208
pubmed: 24385149
Brain Res. 2019 Sep 1;1718:53-63
pubmed: 31026459
Neuron. 2002 Jun 13;34(6):905-19
pubmed: 12086639
Handb Clin Neurol. 2018;154:129-149
pubmed: 29903436
Nat Med. 2011 Oct 16;17(11):1445-7
pubmed: 22001907
J Physiol. 2003 Apr 1;548(Pt 1):53-69
pubmed: 12576503
J Neurosci. 2008 Jul 23;28(30):7599-609
pubmed: 18650337
J Neurosci. 2004 Oct 6;24(40):8818-22
pubmed: 15470147
J Physiol. 2010 Aug 15;588(Pt 16):3031-43
pubmed: 20547676
J Neurosci. 2015 Aug 12;35(32):11292-307
pubmed: 26269637
Neurosci Lett. 1985 Oct 24;61(1-2):49-54
pubmed: 4080260
Cerebellum. 2018 Dec;17(6):735-746
pubmed: 29982917
Nat Neurosci. 2000 Feb;3(2):157-63
pubmed: 10649571
Anat Embryol (Berl). 1991;184(3):225-43
pubmed: 1793166
Neurosurg Rev. 2023 Jul 20;46(1):181
pubmed: 37468768
Front Neural Circuits. 2014 Jan 28;7:96
pubmed: 24478634
J Neurosci. 1997 Apr 15;17(8):2825-38
pubmed: 9092604
Hum Mol Genet. 2020 Nov 25;29(19):3249-3265
pubmed: 32964235
J Neurogenet. 2004 Jan-Mar;18(1):327-39
pubmed: 15370195
Front Neurosci. 2020 Jun 09;14:571
pubmed: 32581696
Front Neural Circuits. 2013 Feb 22;7:1
pubmed: 23440175
J Neurophysiol. 1996 Jul;76(1):255-75
pubmed: 8836223
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
Cerebellum. 2005;4(1):62-73
pubmed: 15895563
J Physiol. 1981 Jun;315:549-67
pubmed: 6273544
Brain Res. 1974 Mar 29;69(1):115-24
pubmed: 4817903
J Neurosci. 2014 Feb 5;34(6):2321-30
pubmed: 24501371
Lancet Neurol. 2010 Sep;9(9):885-94
pubmed: 20723845
J Neurol Sci. 2020 Oct 15;417:117082
pubmed: 32791425
Neurosurgery. 2013 Apr;72(4):573-89; discussion 588-9
pubmed: 23262564
Neuron. 2014 Mar 19;81(6):1389-1400
pubmed: 24656256
Neuron. 2018 Mar 21;97(6):1235-1243.e5
pubmed: 29526553
Neuroscientist. 2007 Dec;13(6):616-25
pubmed: 17911222
Cell. 2006 Dec 29;127(7):1335-47
pubmed: 17190598
J Physiol. 1981 Jun;315:569-84
pubmed: 7310722
J Comp Neurol. 2009 Jul 10;515(2):215-30
pubmed: 19412945
J Neuroophthalmol. 2009 Sep;29(3):227-37
pubmed: 19726947
J Neurosci. 2011 Aug 17;31(33):11795-807
pubmed: 21849540
PLoS One. 2018 May 30;13(5):e0198040
pubmed: 29847609
Br J Pharmacol. 2017 Dec;174 Suppl 1:S360-S446
pubmed: 29055035
J Neurosci Res. 2017 Aug;95(8):1540-1547
pubmed: 27859490
Cerebellum. 2002 Dec;1(4):241-58
pubmed: 12879963
J Neurosci. 1997 Oct 1;17(19):7385-95
pubmed: 9295384
Medicine (Baltimore). 1970 May;49(3):227-41
pubmed: 4910986