دورية أكاديمية
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Dopamine D2 receptors in hilar mossy cells regulate excitatory transmission and hippocampal function.

التفاصيل البيبلوغرافية
العنوان: Dopamine D2 receptors in hilar mossy cells regulate excitatory transmission and hippocampal function.
المؤلفون: Gulfo MC; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461., Lebowitz JJ; Vollum Institute, Oregon Health and Science University, Portland, OR 97239., Ramos C; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461., Hwang DW; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461., Nasrallah K; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461., Castillo PE; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461.; Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY 10461.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Dec 12; Vol. 120 (50), pp. e2307509120. Date of Electronic Publication: 2023 Dec 08.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Epilepsy*/genetics , Epilepsy*/metabolism , Mossy Fibers, Hippocampal*/physiology , Receptors, Dopamine D2*/genetics , Receptors, Dopamine D2*/metabolism, Animals ; Mice ; Dentate Gyrus/metabolism ; Dopamine/metabolism ; Hippocampus/metabolism ; Anxiety/genetics ; Anxiety/metabolism
مستخلص: Hilar mossy cells (MCs) are principal excitatory neurons of the dentate gyrus (DG) that play critical roles in hippocampal function and have been implicated in brain disorders such as anxiety and epilepsy. However, the mechanisms by which MCs contribute to DG function and disease are poorly understood. A defining feature of MCs is the promoter activity of the dopamine D2 receptor (D2R) gene ( Drd2 ), and previous work indicates a key role for dopaminergic signaling in the DG. Additionally, the involvement of D2R signaling in cognition and neuropsychiatric conditions is well known. Surprisingly, though, the function of MC D2Rs remains largely unexplored. In this study, we show that selective and conditional removal of Drd2 from MCs of adult mice impaired spatial memory, promoted anxiety-like behavior, and was proconvulsant. To determine the subcellular expression of D2Rs in MCs, we used a D2R knockin mouse which revealed that D2Rs are enriched in the inner molecular layer of the DG, where MCs establish synaptic contacts with granule cells (GCs). D2R activation by exogenous and endogenous dopamine reduced MC to dentate GC synaptic transmission, most likely by a presynaptic mechanism. In contrast, exogenous dopamine had no significant impact on MC excitatory inputs and passive and active properties. Our findings support that MC D2Rs are essential for proper DG function by reducing MC excitatory drive onto GCs. Lastly, impairment of MC D2R signaling could promote anxiety and epilepsy, therefore highlighting a potential therapeutic target.
Competing Interests: Competing interests statement:The authors declare no competing interest.
التعليقات: Update of: bioRxiv. 2023 May 05:2023.05.05.539468. doi: 10.1101/2023.05.05.539468. (PMID: 37205586)
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معلومات مُعتمدة: R35 GM136296 United States GM NIGMS NIH HHS; T32 DA007262 United States DA NIDA NIH HHS; F31 MH122134 United States MH NIMH NIH HHS; S10 OD025295 United States OD NIH HHS; R01 MH116673 United States MH NIMH NIH HHS; R01 DA004523 United States DA NIDA NIH HHS; R01 NS083085 United States NS NINDS NIH HHS; R01 NS115543 United States NS NINDS NIH HHS; T32 GM007288 United States GM NIGMS NIH HHS; R01 NS113600 United States NS NINDS NIH HHS; F31 MH127910 United States MH NIMH NIH HHS; R01 MH125772 United States MH NIMH NIH HHS
فهرسة مساهمة: Keywords: dentate gyrus; dopamine; hippocampus; memory; mossy cell
المشرفين على المادة: VTD58H1Z2X (Dopamine)
0 (Receptors, Dopamine D2)
0 (DRD2 protein, mouse)
تواريخ الأحداث: Date Created: 20231208 Date Completed: 20231216 Latest Revision: 20240627
رمز التحديث: 20240627
مُعرف محوري في PubMed: PMC10723153
DOI: 10.1073/pnas.2307509120
PMID: 38064513
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.2307509120