Academic Journal
Προβολή σε EDS

Thalamofrontal synaptic weakening underlies short-term memory deficits from adolescent NMDAR hypofunction.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Thalamofrontal synaptic weakening underlies short-term memory deficits from adolescent NMDAR hypofunction.
Συγγραφείς: Yu J; Sensory and Motor Systems Research Group, Korea Brain Research Institute (KBRI), Daegu, Republic of Korea.; Department of Brain Sciences, Daegu Gyeongbuk Institute of Science & Technology (DGIST), Daegu, Republic of Korea., Choi IS; Sensory and Motor Systems Research Group, Korea Brain Research Institute (KBRI), Daegu, Republic of Korea., Kim GH; Neural Circuits Research Group, KBRI, Daegu, Republic of Korea., Bahn S; Cognitive Science Group, KBRI, Daegu, Republic of Korea., Kim J; Department of Electrical Engineering and Computer Science, DGIST, Daegu, Republic of Korea., Bae S; Sensory and Motor Systems Research Group, Korea Brain Research Institute (KBRI), Daegu, Republic of Korea.; Department of Pharmacology, College of Medicine, Yonsei University, Seoul, Republic of Korea., Lee T; Brain Research Core Facility, KBRI, Daegu, Republic of Korea., Choi JH; Sensory and Motor Systems Research Group, Korea Brain Research Institute (KBRI), Daegu, Republic of Korea., Kwon JS; Department of Psychiatry, Hanyang University Hospital, Seoul, Republic of Korea.; Institute of Human Behavioral Medicine, Seoul National University (SNU) Medical Research Center, Seoul, Republic of Korea., Kim M; Institute of Human Behavioral Medicine, Seoul National University (SNU) Medical Research Center, Seoul, Republic of Korea.; Department of Psychiatry, SNU College of Medicine, Seoul, Republic of Korea.; Department of Neuropsychiatry, SNU Hospital, Seoul, Republic of Korea., Choi JW; Department of Electrical Engineering and Computer Science, DGIST, Daegu, Republic of Korea.; Brain Engineering Convergence Research Center, DGIST, Daegu, Republic of Korea.; Biomedical Science and Engineering, DGIST, Daegu, Republic of Korea., Lee KJ; Neural Circuits Research Group, KBRI, Daegu, Republic of Korea., Rah JC; Sensory and Motor Systems Research Group, Korea Brain Research Institute (KBRI), Daegu, Republic of Korea.; Department of Brain Sciences, Daegu Gyeongbuk Institute of Science & Technology (DGIST), Daegu, Republic of Korea.; Brain Engineering Convergence Research Center, DGIST, Daegu, Republic of Korea.; Biomedical Science and Engineering, DGIST, Daegu, Republic of Korea.
Πηγή: Science advances [Sci Adv] 2026 Sep 25; Vol. 12 (39), pp. eaee2152. Date of Electronic Publication: 2026 Sep 23.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE
Imprint Name(s): Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]-
Ιατρικοί όροι (MeSH): Receptors, N-Methyl-D-Aspartate*/metabolism , Receptors, N-Methyl-D-Aspartate*/antagonists & inhibitors , Memory, Short-Term*/drug effects , Memory Disorders*/physiopathology , Memory Disorders*/metabolism , Memory Disorders*/etiology , Synapses*/metabolism , Prefrontal Cortex*/physiopathology , Prefrontal Cortex*/metabolism , Thalamus*/physiopathology , Thalamus*/metabolism, Synaptic Transmission/drug effects ; Ketamine/pharmacology ; Animals ; Mice ; Male
Περίληψη: Thalamofrontal (TF) dysconnectivity is one of the most consistent circuit-level abnormalities reported in patients with schizophrenia and is linked to deficits in short-term memory (STM). However, the biological mechanisms underlying TF weakening remain unclear. Here, we show that repeated adolescent N-methyl-d-aspartate receptor (NMDAR) antagonism produces STM deficits by impairing TF synaptic transmission. In mice repeatedly exposed to ketamine, STM impairment coincided with reduced release probability and attenuated short-term depression at mediodorsal thalamus (MD) → dorsomedial prefrontal cortex (dmPFC) synapses, without detectable changes in corticocortical synaptic release probability, intrinsic excitability, or gross synaptic ultrastructure. These presynaptic deficits were accompanied by diminished direction-selective population coding in the dmPFC and impaired delayed alternation performance. Chemogenetically strengthening MD → dmPFC projections restored both neural selectivity and behavior. These findings identify a projection-specific presynaptic mechanism through which adolescent NMDAR hypofunction weakens TF communication and produces cognitive impairment, offering a biological explanation for clinically observed TF dysconnectivity and establishing TF synapses as a therapeutic target.
References: Neuron. 1996 Jun;16(6):1197-207. (PMID: 8663996)
Nat Neurosci. 2017 Jul;20(7):987-996. (PMID: 28481349)
Neuron. 1995 Mar;14(3):477-85. (PMID: 7695894)
Arch Gen Psychiatry. 2003 Jun;60(6):572-6. (PMID: 12796220)
J Neurosci. 2007 Oct 24;27(43):11496-500. (PMID: 17959792)
Curr Opin Pharmacol. 2007 Feb;7(1):48-55. (PMID: 17097347)
Am J Psychiatry. 1999 Sep;156(9):1358-66. (PMID: 10484945)
Mol Psychiatry. 2021 Jun;26(6):2562-2576. (PMID: 32382134)
Biol Psychiatry. 2010 May 15;67(10):926-32. (PMID: 20034612)
Front Cell Neurosci. 2023 Jul 13;17:1153970. (PMID: 37519632)
Trends Neurosci. 2010 Jun;33(6):259-66. (PMID: 20371122)
Biol Psychiatry. 2015 Sep 15;78(6):361-73. (PMID: 25662103)
Annu Rev Neurosci. 2024 Aug;47(1):41-61. (PMID: 38382543)
Nature. 2017 May 11;545(7653):219-223. (PMID: 28467827)
Nat Protoc. 2013 Dec;8(12):2531-7. (PMID: 24263092)
Neuron. 2010 Dec 9;68(5):907-20. (PMID: 21145004)
PLoS One. 2007 Aug 08;2(8):e700. (PMID: 17684547)
J Comput Neurosci. 1998 Dec;5(4):383-405. (PMID: 9877021)
Neuropsychology. 2008 Sep;22(5):606-17. (PMID: 18763880)
EMBO J. 1999 Aug 16;18(16):4372-82. (PMID: 10449403)
Biol Psychol. 2016 Apr;116:57-67. (PMID: 26549579)
Cell. 1999 Aug 20;98(4):427-36. (PMID: 10481908)
BMC Res Notes. 2010 May 27;3:149. (PMID: 20507606)
Neuropsychopharmacology. 2004 Jun;29(6):1203-14. (PMID: 15100698)
Methods Mol Biol. 2019;1916:105-111. (PMID: 30535688)
Schizophr Bull. 2007 Jul;33(4):1038-53. (PMID: 17093141)
PLoS Biol. 2025 Sep 3;23(9):e3003359. (PMID: 40901919)
J Neurosci. 1999 Nov 1;19(21):9587-603. (PMID: 10531461)
J Neurophysiol. 2004 Sep;92(3):1738-55. (PMID: 15140911)
Ann N Y Acad Sci. 2003 Nov;1003:318-27. (PMID: 14684455)
Science. 1995 Aug 18;269(5226):981-5. (PMID: 7638624)
ACS Pharmacol Transl Sci. 2018 Sep 14;1(1):61-72. (PMID: 30868140)
J Neurophysiol. 1992 Jul;68(1):345-9. (PMID: 1381421)
Sci Rep. 2019 Mar 14;9(1):4522. (PMID: 30872749)
Physiol Behav. 2007 Sep 10;92(1-2):203-9. (PMID: 17573079)
Am J Psychiatry. 2012 Oct;169(10):1092-9. (PMID: 23032387)
Behav Brain Res. 2017 Aug 14;332:316-326. (PMID: 28634108)
Neuropsychopharmacology. 2024 Mar;49(4):720-730. (PMID: 38049583)
PLoS One. 2017 Dec 18;12(12):e0189287. (PMID: 29253020)
Nature. 2015 Jun 18;522(7556):309-14. (PMID: 26053122)
Neuron. 2013 Mar 20;77(6):1151-62. (PMID: 23522049)
Front Hum Neurosci. 2015 Jan 09;8:1027. (PMID: 25620923)
Schizophr Bull. 1998;24(2):203-18. (PMID: 9613621)
Nat Neurosci. 2025 Jul;28(7):1404-1417. (PMID: 40425792)
AMA Arch Neurol Psychiatry. 1959 Mar;81(3):363-9. (PMID: 13626287)
Cell. 2021 Jul 22;184(15):4048-4063.e32. (PMID: 34233165)
eNeuro. 2024 Aug 29;11(8):. (PMID: 39134414)
J Neurosci. 2015 Apr 8;35(14):5743-53. (PMID: 25855185)
Arch Gen Psychiatry. 2012 Aug;69(8):766-74. (PMID: 22474071)
Neuron. 2013 Oct 16;80(2):335-42. (PMID: 24139038)
Nature. 1993 Oct 21;365(6448):753-6. (PMID: 8413653)
Schizophr Bull. 2012 Sep;38(5):920-6. (PMID: 22987850)
Elife. 2016 Nov 16;5:. (PMID: 27849520)
Elife. 2021 May 05;10:. (PMID: 33949949)
Cell Rep Med. 2024 Nov 19;5(11):101802. (PMID: 39515319)
Cereb Cortex. 2000 Sep;10(9):910-23. (PMID: 10982751)
Biol Psychiatry. 1996 Nov 1;40(9):930-2. (PMID: 8896783)
Neuron. 2005 Oct 20;48(2):315-27. (PMID: 16242411)
Brain. 2025 May 13;148(5):1652-1664. (PMID: 40071389)
Nature. 2017 May 11;545(7653):181-186. (PMID: 28467817)
Mol Psychiatry. 2022 Jan;27(1):731-743. (PMID: 34163013)
Prog Neurobiol. 2025 Jun;249:102761. (PMID: 40258455)
Mol Psychiatry. 2022 Jan;27(1):281-295. (PMID: 34079068)
Nature. 1999 Oct 7;401(6753):594-8. (PMID: 10524627)
Neuroscience. 2002;114(3):769-79. (PMID: 12220577)
J Neurosci. 2025 Sep 17;45(38):. (PMID: 40829937)
Arch Gen Psychiatry. 1994 Mar;51(3):199-214. (PMID: 8122957)
J Pharmacol Exp Ther. 2006 Jan;316(1):315-24. (PMID: 16192313)
Annu Rev Neurosci. 2017 Jul 25;40:603-627. (PMID: 28772102)
Science. 2008 Sep 12;321(5895):1507-10. (PMID: 18703708)
Neurosci Biobehav Rev. 2022 Apr;135:104560. (PMID: 35124156)
J Neurosci. 2005 Dec 14;25(50):11655-65. (PMID: 16354924)
Mol Brain. 2020 May 6;13(1):68. (PMID: 32375833)
Neuron. 1999 Jun;23(2):399-409. (PMID: 10399944)
Schizophr Res. 2010 Jun;119(1-3):198-209. (PMID: 20347576)
Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8467-72. (PMID: 15159546)
Nat Struct Mol Biol. 2010 Mar;17(3):280-8. (PMID: 20154707)
Nature. 1999 Jun 3;399(6735):470-3. (PMID: 10365959)
J Neurosci. 2006 Apr 26;26(17):4535-45. (PMID: 16641233)
Substance Nomenclature: 0 (Receptors, N-Methyl-D-Aspartate)
690G0D6V8H (Ketamine)
Entry Date(s): Date Created: 20260923 Date Completed: 20260923 Latest Revision: 20260925
Update Code: 20260925
PubMed Central ID: PMC13600250
DOI: 10.1126/sciadv.aee2152
PMID: 42777060
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2375-2548
DOI:10.1126/sciadv.aee2152