Deep within the developing mammalian brain, a temporary structure known as the ganglionic eminence (GE) appears during fetal development. Located in the ventral part of the embryonic forebrain, or telencephalon, the GE acts as a biological factory, generating a diverse population of neurons and other cells. These newly formed cells then migrate to populate various regions of the growing brain. Their successful production and deployment are important for the brain’s future architecture and function.
Anatomical Subdivisions and Cell Production
The ganglionic eminence is composed of three distinct anatomical subdivisions: the medial (MGE), lateral (LGE), and caudal (CGE) ganglionic eminences. Each region is a specialized hub of cellular production, giving rise to different types of cells that will integrate into complex neural circuits.
The medial ganglionic eminence is the primary source of neurons that use the neurotransmitter GABA. These GABAergic interneurons are the main inhibitory cells in the brain. The MGE produces the majority of interneurons destined for the cerebral cortex and also generates neurons that will become part of the globus pallidus, a structure involved in regulating movement.
The lateral ganglionic eminence (LGE) is the main production site for the projection neurons of the striatum, a brain region central to motor control and reward. These neurons differ from MGE interneurons as they send messages over longer distances. The LGE also contributes interneurons to the olfactory bulb, the brain’s primary center for processing smells, and to the cortex.
Finally, the caudal ganglionic eminence (CGE) specializes in producing other specific subtypes of cortical interneurons not generated by the MGE.
Beyond neurons, the GE is also a source of oligodendrocytes. These are non-neuronal cells that produce myelin, the fatty sheath that insulates nerve fibers and allows for rapid communication between brain cells.
Neuronal Migration from the Ganglionic Eminence
Once produced in the ganglionic eminence, new neurons begin a guided journey to their final destinations in a process called tangential migration. This form of migration is distinct because the cells travel long distances, moving parallel to the surface of the developing brain to reach sites like the cerebral cortex, striatum, and hippocampus.
This tangential pathway contrasts with another form of cell movement known as radial migration. During radial migration, excitatory neurons born in a different brain region climb along scaffolding-like glial cells to form the layered structure of the cortex. The GE-derived interneurons, however, travel perpendicularly to these radial glial cells, navigating a sideways route.
The journey is not random; it is guided by a system of molecular cues. An array of motogenic growth factors within the MGE helps to initiate movement. As the cells travel, they are pushed by repulsive factors and guided by permissive factors in migratory corridors. Upon approaching their final destination, attractive factors draw them in, ensuring they settle in the correct location.
This process of tangential migration is a defining feature of forebrain development. It ensures that inhibitory interneurons produced in the ventral forebrain can be distributed throughout the dorsal regions where the cortex is forming, establishing necessary cellular diversity.
Role in Cortical Development and Function
The arrival of GABAergic interneurons from the ganglionic eminence into the cerebral cortex is an important event in brain development. These cells are the primary architects of the brain’s inhibitory system. Their integration among excitatory neurons establishes the excitatory-inhibitory (E/I) balance, which is important for nearly all aspects of brain function.
The brain’s ability to process information relies on this interplay between excitation and inhibition. Excitatory neurons pass signals along, while inhibitory interneurons act as “stop” signals, refining neural activity. Without this inhibition, the cortex would experience uncontrolled firing, making organized thought or coordinated action impossible.
By releasing the neurotransmitter GABA, these interneurons dampen the activity of excitatory cells, preventing over-excitation and ensuring that neural communication is precise. This regulatory role supports the complex computations underlying higher cognitive functions, including learning, memory, and sensory processing. The proper E/I balance allows neural circuits to operate with high fidelity.
The distribution and function of these GE-derived interneurons also lay the groundwork for the brain’s capacity for plasticity. They help shape critical periods in development when the brain is particularly sensitive to experience and continue to regulate information flow throughout life.
Implications in Neurological Disorders
Because the ganglionic eminence is important for populating the brain with inhibitory interneurons, disruptions to its development can have significant consequences. Errors in the production, migration, or maturation of these GABAergic cells can upset the brain’s excitatory-inhibitory balance. This imbalance is a contributing factor to several neurodevelopmental and psychiatric conditions.
For instance, epilepsy is a disorder characterized by recurrent seizures, which are storms of abnormal electrical activity in the brain. A leading hypothesis for some forms of epilepsy is a deficit in cortical inhibition. If the GE fails to produce enough interneurons, or if these cells fail to migrate correctly, the brain’s “stop” signals can be too weak, leading to the hyperexcitability that manifests as seizures.
Imbalances in the E/I ratio have also been implicated in schizophrenia and autism spectrum disorder. In these conditions, altered signaling is thought to affect cognitive functions, social processing, and sensory perception. A disruption in the precise timing and pattern of inhibitory signaling may contribute to difficulties with information processing and social interaction.
Research into the ganglionic eminence continues to clarify the developmental origins of these conditions. Anomalies in the GE’s structure, sometimes visible on fetal MRIs, have been associated with a range of neurodevelopmental issues. Understanding the link between this embryonic structure and adult brain function provides a window into the causes of these disorders and may inform new intervention strategies.