Presenilins regulate synaptic plasticity in the perforant pathways of the hippocampus.
Alzheimer’s disease
Calcium homeostasis
Conditional knockout
Hippocampus
Long-term potentiation
Perforant pathways
Short-term synaptic plasticity
Journal
Molecular brain
ISSN: 1756-6606
Titre abrégé: Mol Brain
Pays: England
ID NLM: 101468876
Informations de publication
Date de publication:
30 01 2023
30 01 2023
Historique:
received:
17
10
2022
accepted:
20
01
2023
entrez:
30
1
2023
pubmed:
31
1
2023
medline:
1
2
2023
Statut:
epublish
Résumé
Mutations in the Presenilin genes (PSEN1 and PSEN2) are the major cause of familial Alzheimer's disease (AD), highlighting the importance of Presenilin (PS) in AD pathogenesis. Previous studies of PS function in the hippocampus demonstrated that loss of PS results in the impairment of short- and long-term synaptic plasticity and neurotransmitter release at hippocampal Schaffer collateral (SC) and mossy fiber (MF) synapses. Cortical input to the hippocampus through the lateral perforant pathway (LPP) and the medial perforant pathway (MPP) is critical for normal cognitive functions and is particularly vulnerable during aging and early stages of AD. Whether PS regulates synaptic function in the perforant pathways, however, remained unknown. In the current study, we investigate PS function in the LPP and MPP by performing whole-cell and field-potential electrophysiological recordings using acute hippocampal slices from postnatal forebrain-restricted excitatory neuron-specific PS conditional double knockout (cDKO) mice. We found that paired-pulse ratio (PPR) is reduced in the LPP and MPP of PS cDKO mice. Moreover, synaptic frequency facilitation or depression in the LPP or MPP, respectively, is impaired in PS cDKO mice. Notably, depletion of intracellular Ca
Identifiants
pubmed: 36710361
doi: 10.1186/s13041-023-01009-x
pii: 10.1186/s13041-023-01009-x
pmc: PMC9885562
doi:
Substances chimiques
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
17Subventions
Organisme : NIA NIH HHS
ID : RF1 AG063520
Pays : United States
Organisme : NINDS NIH HHS
ID : RF1 NS041783
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS041783
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS101745
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH108665
Pays : United States
Organisme : NINDS NIH HHS
ID : NS041783
Pays : United States
Organisme : NINDS NIH HHS
ID : AG063520
Pays : United States
Informations de copyright
© 2023. The Author(s).
Références
J Neurochem. 1999 Mar;72(3):1061-8
pubmed: 10037477
Neuron. 2001 Jan;29(1):197-208
pubmed: 11182091
Neuron. 1992 Jul;9(1):79-84
pubmed: 1321647
Annu Rev Neurosci. 1998;21:127-48
pubmed: 9530494
Neuroscience. 1989;31(3):571-91
pubmed: 2687721
Mol Neurodegener. 2008 Jan 08;3:2
pubmed: 18182109
Neuron. 2010 Nov 4;68(3):428-41
pubmed: 21040845
Neuron. 2002 Oct 24;36(3):507-19
pubmed: 12408852
J Cell Biol. 2008 Jun 30;181(7):1107-16
pubmed: 18591429
Neuron. 2002 Dec 19;36(6):1103-14
pubmed: 12495625
Mol Neurodegener. 2017 Jun 15;12(1):48
pubmed: 28619096
Neuron. 2015 Mar 4;85(5):967-81
pubmed: 25741723
Behav Neurosci. 2007 Aug;121(4):742-50
pubmed: 17663599
Ann Neurol. 2001 Feb;49(2):202-13
pubmed: 11220740
Neuron. 2004 Apr 8;42(1):23-36
pubmed: 15066262
J Neurosci. 2016 Jan 13;36(2):350-63
pubmed: 26758828
Nat Rev Neurosci. 2002 Mar;3(3):175-90
pubmed: 11994750
PLoS One. 2012;7(2):e31302
pubmed: 22312444
Nat Cell Biol. 2009 Jul;11(7):909-13
pubmed: 19503072
Nature. 1993 Jan 7;361(6407):31-9
pubmed: 8421494
Neuron. 2001 Sep 13;31(5):713-26
pubmed: 11567612
Cereb Cortex. 2013 Feb;23(2):451-9
pubmed: 22357665
Pflugers Arch. 2014 Jul;466(7):1437-50
pubmed: 24132829
Ann Neurol. 1986 Oct;20(4):472-81
pubmed: 3789663
Arch Neurol. 2001 Sep;58(9):1395-402
pubmed: 11559310
Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11998-2003
pubmed: 18687898
Neurology. 2007 Sep 4;69(10):986-97
pubmed: 17785667
J Neurosci. 2003 Dec 3;23(35):11229-34
pubmed: 14657182
J Biol Chem. 2009 May 15;284(20):13705-13713
pubmed: 19289467
Prog Neurobiol. 2003 Apr;69(6):391-418
pubmed: 12880633
Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):14825-6
pubmed: 23995445
Brain Res. 1980 Oct 13;199(1):1-19
pubmed: 7407615
Exp Neurol. 2000 May;163(1):98-110
pubmed: 10785448
Neurology. 2003 Dec 9;61(11):1491-7
pubmed: 14663030
J Neurosci. 2005 Jan 19;25(3):558-65
pubmed: 15659591
Development. 2000 Jun;127(12):2593-606
pubmed: 10821758
J Physiol. 2001 Mar 15;531(Pt 3):807-26
pubmed: 11251060
Nature. 2009 Jul 30;460(7255):632-6
pubmed: 19641596
PLoS One. 2010 Apr 15;5(4):e10195
pubmed: 20419112
J Neurophysiol. 2003 Jun;89(6):3029-38
pubmed: 12783948
Cell. 1994 Aug 26;78(4):535-8
pubmed: 8069904
CNS Spectr. 2019 Feb;24(1):78-87
pubmed: 30651152
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4702-7
pubmed: 9539802
J Neurosci. 1996 Jul 15;16(14):4491-500
pubmed: 8699259
J Neurophysiol. 1993 Apr;69(4):1150-9
pubmed: 8492154
Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):15091-6
pubmed: 23918386
Cell. 2006 Sep 8;126(5):981-93
pubmed: 16959576
Nat Rev Neurosci. 2006 Apr;7(4):278-94
pubmed: 16552414
Mol Neurodegener. 2020 Dec 10;15(1):72
pubmed: 33302995
Neural Plast. 2010;2010:108190
pubmed: 21331296
Neurosci Res. 1992 Oct;15(1-2):6-31
pubmed: 1336586
Cell. 1997 May 16;89(4):629-39
pubmed: 9160754
Trends Neurosci. 2008 Sep;31(9):454-63
pubmed: 18675468
Mol Brain. 2021 May 25;14(1):85
pubmed: 34034776
Sci Rep. 2017 Feb 13;7:42370
pubmed: 28205565
J Biol Chem. 2004 Nov 5;279(45):46907-14
pubmed: 15345711
Neurobiol Aging. 2006 Oct;27(10):1372-84
pubmed: 16289476
J Neurophysiol. 2003 Jul;90(1):32-8
pubmed: 12634277
J Neurosci. 2016 Jan 13;36(2):312-24
pubmed: 26758825
J Neurochem. 2010 Dec;115(5):1215-21
pubmed: 20854432
Dementia. 1996 Jul-Aug;7(4):226-32
pubmed: 8835888
Dev Biol. 2005 Jan 15;277(2):332-46
pubmed: 15617678
Neurobiol Aging. 2015 Mar;36(3):1303-9
pubmed: 25554494
Trends Pharmacol Sci. 1998 Apr;19(4):131-5
pubmed: 9612087
Neurology. 2002 Jun 25;58(12):1791-800
pubmed: 12084879
J Physiol. 2000 Jun 1;525 Pt 2:405-18
pubmed: 10835043
J Biol Chem. 2012 Mar 30;287(14):10933-44
pubmed: 22311977
Cereb Cortex. 1991 Jan-Feb;1(1):103-16
pubmed: 1822725