The brain's nerve cells are functionally categorized into two main types: 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 neurons or distant regions. These cells often share similar morphological features, electrophysiological properties, and synaptic connections within the same brain area.
Interneurons, on the other hand, are located in proximity to these principal cells and have axons that remain confined to a single brain region. Their primary role is to modulate the activity of principal neurons by providing inhibitory signals. Unlike the relatively uniform excitatory neurons, interneurons exhibit a remarkable diversity in their structure, molecular markers, electrical properties, and connectivity patterns. This variability, known as interneuronal diversity, allows them to play specialized roles in different parts of the brain.
Many interneurons migrate long distances during development to reach the cerebral cortex. Once there, they establish local connections. Research has shown that only interneurons from the medial ganglionic eminence (MGE) can successfully complete this long journey. When compared to lateral ganglionic eminence (LGE) neurons, which remain clustered after transplantation, MGE-derived interneurons spread out and integrate into the cortical network.
Importantly, transplanted interneurons follow intrinsic developmental programs without needing host-specific signals to survive or differentiate. This suggests that their fate is largely determined by internal genetic instructions rather than external cues. After reaching the cortex, these young interneurons develop into various types of inhibitory neurons, with about two-thirds surviving to form local inhibitory circuits. The entire process—migration, survival, and integration—is guided by the embryo’s developmental blueprint.
Finally, the researchers emphasize that cortical interneurons represent a highly heterogeneous group. The specific functions of different subtypes in 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 more specific cell populations for therapeutic applications. This could lead to more targeted treatments for neurological disorders involving impaired inhibition.