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Inhibitory Synapse Formation in a Co-culture Model Incorporating GABAergic Medium Spiny Neurons and HEK293 Cells Stably Expressing GABAA Receptors

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Early GABAergic circuitry in the cerebral cortex.

Heiko J Luhmann¹, Sergei Kirischuk¹, Anne Sinning¹

¹Institute of Physiology, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.

Current Opinion in Neurobiology

|January 18, 2014

Summary

GABAergic signaling is crucial for brain development, influencing neuron growth and migration. Its role in network activity matures over time, shifting from minor to significant influence as the brain develops.

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Published on: August 16, 2018

Area of Science:

Neuroscience
Developmental Biology
Cellular Signaling

Background:

GABAergic signaling is vital for early cerebral cortex development, including neurogenesis, migration, and differentiation.
Transient neuronal populations like Cajal-Retzius cells and subplate neurons participate in early GABAergic circuits.
Immature pyramidal neurons receive GABAergic inputs early but join functional circuits later, limiting early network influence.

Purpose of the Study:

To investigate the role and developmental trajectory of GABAergic signaling in the cerebral cortex.
To understand how GABAergic transmission influences spontaneous network activity during corticogenesis.
To elucidate the shift in GABA's function from excitatory to inhibitory during cortical maturation.

Main Methods:

Analysis of GABAergic synaptic inputs on developing pyramidal neurons.
Observation of network activity during early corticogenesis.
Tracking the developmental shift in GABA's functional role.

Main Results:

GABAergic synaptic transmission has minimal impact on spontaneous network activity in early corticogenesis.
Immature pyramidal neurons integrate into functional GABAergic circuits days after receiving initial inputs.
GABA gains importance in synchronizing neuronal network activity as the cortex matures and GABA shifts to inhibition.

Conclusions:

GABAergic signaling's influence on cortical network activity evolves significantly during development.
The shift of GABA from excitatory to inhibitory action is critical for its role in network synchronization.
Understanding these developmental dynamics is key to comprehending normal and aberrant brain function.