d-serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturation
Abstract The proper development and function of telencephalic GABAergic interneurons is critical for maintaining the excitation and inhibition (E/I) balance in cortical circuits. Glutamate contributes to cortical interneuron (CIN) development via N-methyl-d-aspartate receptors (NMDARs). NMDAR activa...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-35615-5 |
| _version_ | 1797801463716511744 |
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| author | Oluwarotimi O. Folorunso Stephanie E. Brown Jugajyoti Baruah Theresa L. Harvey Shekib A. Jami Inna Radzishevsky Herman Wolosker James M. McNally John A. Gray Anju Vasudevan Darrick T. Balu |
| author_facet | Oluwarotimi O. Folorunso Stephanie E. Brown Jugajyoti Baruah Theresa L. Harvey Shekib A. Jami Inna Radzishevsky Herman Wolosker James M. McNally John A. Gray Anju Vasudevan Darrick T. Balu |
| author_sort | Oluwarotimi O. Folorunso |
| collection | DOAJ |
| description | Abstract The proper development and function of telencephalic GABAergic interneurons is critical for maintaining the excitation and inhibition (E/I) balance in cortical circuits. Glutamate contributes to cortical interneuron (CIN) development via N-methyl-d-aspartate receptors (NMDARs). NMDAR activation requires the binding of a co-agonist, either glycine or d-serine. d-serine (co-agonist at many mature forebrain synapses) is racemized by the neuronal enzyme serine racemase (SR) from l-serine. We utilized constitutive SR knockout (SR−/−) mice to investigate the effect of d-serine availability on the development of CINs and inhibitory synapses in the prelimbic cortex (PrL). We found that most immature Lhx6 + CINs expressed SR and the obligatory NMDAR subunit NR1. At embryonic day 15, SR−/− mice had an accumulation of GABA and increased mitotic proliferation in the ganglionic eminence and fewer Gad1 + (glutamic acid decarboxylase 67 kDa; GAD67) cells in the E18 neocortex. Lhx6 + cells develop into parvalbumin (PV+) and somatostatin (Sst+) CINs. In the PrL of postnatal day (PND) 16 SR−/− mice, there was a significant decrease in GAD67+ and PV+, but not SST + CIN density, which was associated with reduced inhibitory postsynaptic potentials in layer 2/3 pyramidal neurons. These results demonstrate that D-serine availability is essential for prenatal CIN development and postnatal cortical circuit maturation. |
| first_indexed | 2024-03-13T04:50:51Z |
| format | Article |
| id | doaj.art-c1a3de421db14b62abea4c8f005bf011 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T04:50:51Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c1a3de421db14b62abea4c8f005bf0112023-06-18T11:12:29ZengNature PortfolioScientific Reports2045-23222023-06-0113111110.1038/s41598-023-35615-5d-serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturationOluwarotimi O. Folorunso0Stephanie E. Brown1Jugajyoti Baruah2Theresa L. Harvey3Shekib A. Jami4Inna Radzishevsky5Herman Wolosker6James M. McNally7John A. Gray8Anju Vasudevan9Darrick T. Balu10Division of Basic Neuroscience, McLean HospitalDivision of Basic Neuroscience, McLean HospitalDivision of Basic Neuroscience, McLean HospitalDivision of Basic Neuroscience, McLean HospitalCenter for Neuroscience, University of California DavisDepartment of Biochemistry, Rappaport Faculty of Medicine, Technion-Israel Institute of TechnologyDepartment of Biochemistry, Rappaport Faculty of Medicine, Technion-Israel Institute of TechnologyDepartment of Psychiatry, Harvard Medical SchoolCenter for Neuroscience, University of California DavisAngiogenesis and Brain Development Laboratory, Department of Neurosciences, Huntington Medical Research Institutes (HMRI)Division of Basic Neuroscience, McLean HospitalAbstract The proper development and function of telencephalic GABAergic interneurons is critical for maintaining the excitation and inhibition (E/I) balance in cortical circuits. Glutamate contributes to cortical interneuron (CIN) development via N-methyl-d-aspartate receptors (NMDARs). NMDAR activation requires the binding of a co-agonist, either glycine or d-serine. d-serine (co-agonist at many mature forebrain synapses) is racemized by the neuronal enzyme serine racemase (SR) from l-serine. We utilized constitutive SR knockout (SR−/−) mice to investigate the effect of d-serine availability on the development of CINs and inhibitory synapses in the prelimbic cortex (PrL). We found that most immature Lhx6 + CINs expressed SR and the obligatory NMDAR subunit NR1. At embryonic day 15, SR−/− mice had an accumulation of GABA and increased mitotic proliferation in the ganglionic eminence and fewer Gad1 + (glutamic acid decarboxylase 67 kDa; GAD67) cells in the E18 neocortex. Lhx6 + cells develop into parvalbumin (PV+) and somatostatin (Sst+) CINs. In the PrL of postnatal day (PND) 16 SR−/− mice, there was a significant decrease in GAD67+ and PV+, but not SST + CIN density, which was associated with reduced inhibitory postsynaptic potentials in layer 2/3 pyramidal neurons. These results demonstrate that D-serine availability is essential for prenatal CIN development and postnatal cortical circuit maturation.https://doi.org/10.1038/s41598-023-35615-5 |
| spellingShingle | Oluwarotimi O. Folorunso Stephanie E. Brown Jugajyoti Baruah Theresa L. Harvey Shekib A. Jami Inna Radzishevsky Herman Wolosker James M. McNally John A. Gray Anju Vasudevan Darrick T. Balu d-serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturation Scientific Reports |
| title | d-serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturation |
| title_full | d-serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturation |
| title_fullStr | d-serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturation |
| title_full_unstemmed | d-serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturation |
| title_short | d-serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturation |
| title_sort | d serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturation |
| url | https://doi.org/10.1038/s41598-023-35615-5 |
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