Excitatory and inhibitory synapses show a tight subcellular correlation that weakens over development
Sally Horton1, Vincenzo Mastrolia1, Rachel E Jackson1
1MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK; Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK.
Cell Reports
|June 20, 2024
Summary
Developing neurons establish a strong balance between excitatory and inhibitory synapses early on. This crucial synaptic balance, vital for brain function, diminishes as neurons mature.
Area of Science:
- Neuroscience
- Developmental Biology
- Synaptic Plasticity
Background:
- Neurons require balanced excitation and inhibition for proper brain function.
- The developmental mechanisms establishing this excitatory-inhibitory (E/I) balance are largely unknown.
Purpose of the Study:
- To investigate how the relationship between excitatory and inhibitory inputs is established during neuronal development.
- To explore the spatial distribution and temporal dynamics of E/I synapses in developing hippocampal neurons.
Main Methods:
- In utero electroporation for genetic manipulation of developing neurons.
- Electron microscopy for ultrastructural analysis of synapses.
- Electrophysiology to assess neuronal activity and synaptic function.
Main Results:
- A tight correlation was observed in the distribution of excitatory and inhibitory synapses along developing CA1 hippocampal neuron dendrites.
- This E/I synaptic correlation was most pronounced during early development and decreased with neuronal maturation.
- Newly formed inhibitory synapses showed immature features, lacking active zones and exhibiting compromised release, yet contributed to E/I balance.
Conclusions:
- Inhibitory synapses may initially form as a scaffold to stabilize developing neuronal circuits by counterbalancing excitation.
- The dynamic E/I balance during early development plays a critical role in neuronal function and circuit formation.
- The observed decline in E/I correlation suggests a shift in synaptic regulation as circuits mature.
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