D-serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturation.
Oluwarotimi O Folorunso1,2, Stephanie E Brown3, Jugajyoti Baruah3,4
1Division of Basic Neuroscience, McLean Hospital, Belmont, MA, 02478, USA. ofolorunso@mclean.harvard.edu.
Scientific Reports
|June 13, 2023
Summary
D-serine is crucial for developing cortical interneurons and maintaining brain excitation-inhibition balance. Serine racemase knockout mice show impaired interneuron development and function, highlighting D-serine
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Synaptic Plasticity
Background:
- Cortical circuit function relies on balanced excitation and inhibition (E/I), primarily mediated by GABAergic interneurons.
- Glutamate signaling via N-methyl-D-aspartate receptors (NMDARs) is vital for interneuron development.
- D-serine, a co-agonist for NMDARs, is synthesized by serine racemase (SR).
Purpose of the Study:
- To investigate the role of D-serine availability in the development of cortical interneurons (CINs) and inhibitory synapses.
- To examine the impact of serine racemase deficiency on the prenatal and postnatal development of the prelimbic cortex (PrL).
Main Methods:
- Utilized constitutive serine racemase knockout (SR-/-) mice.
- Analyzed GABAergic interneuron markers (Lhx6, GAD67, PV, Sst) and NMDAR subunit NR1 expression.
- Assessed cell proliferation and synaptic function (inhibitory postsynaptic potentials) in the PrL.
Main Results:
- SR-/- mice exhibited altered GABA levels and increased proliferation in the ganglionic eminence during embryonic development.
- A significant reduction in GAD67+ and parvalbumin (PV)+ interneuron density was observed in the PrL of SR-/- mice.
- SR deficiency led to diminished inhibitory postsynaptic potentials in layer 2/3 pyramidal neurons.
Conclusions:
- D-serine availability is essential for proper prenatal development of cortical interneurons.
- Adequate D-serine levels are critical for the maturation of postnatal cortical circuits and synaptic function.
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