In brain tissue, nerve cells are functionally categorized into two main groups: excitatory principal neurons and interneurons. Excitatory principal cells are responsible for synthesizing and releasing glutamate, integrating multiple synaptic inputs, and transmitting neuronal signals to downstream effector cells such as muscles or glands. These cells typically share similar structural features, electrophysiological properties, and synaptic connections within the same brain region.
Interneurons, on the other hand, are located in close proximity to these principal cells. Their axons remain confined to a specific brain area, and they play a key role in modulating the activity of the principal neurons. Unlike the relatively uniform excitatory neurons, interneurons exhibit a remarkable diversity in shape, molecular markers, electrical behavior, and connectivity. Even within the same brain region, interneurons can differ significantly in their distribution and functional roles, a phenomenon known as interneuronal diversity.
These interneurons have the ability to migrate long distances during development, ultimately reaching the cerebral cortex. Once there, they establish local connections. Research has shown that only interneurons originating from the medial ganglionic eminence (MGE) can successfully complete this long journey. When transplanted into the postnatal brain, LGE-derived neurons remain clustered, while MGE-derived neurons spread out across the cortex.
Importantly, transplanted interneurons follow their own intrinsic developmental program without needing external host signals to guide their survival or differentiation. This suggests that traditional views about neurotrophic factors and competitive survival may not fully apply here. After migrating to the developing brain, young interneurons reach the cortex and differentiate into various types of inhibitory neurons. Approximately two-thirds of them survive and integrate into local inhibitory circuits, guided by an embryonic program that controls their migration, survival, and integration into neural networks.
Finally, the authors emphasize that cortical interneurons form a highly heterogeneous population. The exact roles of different interneuron subtypes within neural circuits remain unclear. Current transplantation studies often use mixed populations of donor interneurons. As our understanding of interneuronal diversity deepens, it may become possible to isolate or generate donor cell populations containing only specific subtypes, opening new possibilities for targeted therapeutic applications.
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