Mercedes Paredes, MD, PhD

Assistant Professor
Neurology

Late Cortical Neuron Development in the Human Brain and Neurodevelopmental Disorders

Inhibitory neurons, or interneurons, make up ~20% of the neuronal population in the neocortex, the area associated with higher brain functions. Yet they have great diversity in composition and function, including maintaining the balance of excitation and inhibition in the brain.  Abnormalities in interneuron development have been associated with neurological disorders such as epilepsy and intellectual delay.  Interneurons are born in different regions of the embryonic brain.  These progenitor niches are known as the ganglionic eminences (GE).  Interneurons born in different parts of the GE express unique regional transcription factors and become different subtypes of interneurons. Interneurons born in the medial GE (MGE) express Nkx2.1 and LHX6 later and most become either parvalbumin (PV) or somatostatin (SST) expressing neurons. Interneurons born in the lateral or caudal GE (LGE or CGE) express CoupTFII and Sp8 and tend to become calretinin (CR) or neuropeptide Y (NPY) expressing neurons; they can also express markers such as RLN and vasoactive intestinal peptide (VIP).  We recently published evidence of robust migration of interneurons in the postnatal human brain. This collection of late-migrating interneurons contributes to the cortical network during the first months of life, specifically in the prefrontal cortex and cingulate.  The presence of the “Arc” goes against the presumption that most of neuronal migration is complete by birth.  It also supports the theory that the human brain undergoes a protracted development, especially in areas of higher cognition, and offers one mechanism by which the frontal cortex may have grown in size and complexity.  Given that frontal lobe pathology has been implicated in neuropsychiatric disorders, disruption in its postnatal development may also lead to neurodevelopmental disease.

Current Projects

1:  To identify the diversity within postnatally migrating inhibitory neurons in the human frontal lobe.  
2: To define the source of postnatally migrating interneurons in the forebrain using large animal models such as the macaque and pig brains.

Lab Members

Kadellyn Sandoval
Staff Research Associate
[email protected]

Quetzal Flores
Junior Specialist
[email protected]