Yale Researchers Trace Embryonic Origin of Key Neurons in the Brain

Yale researchers have discovered a new clump of human brain cells that differ from those of other mammals and may offer clues as to the source of certain mental diseases and disorders, according to an article published this week in the journal Nature.

Pasko Rakic, professor and chair of the Department of Neurobiology at Yale School of Medicine, and his colleagues, traced the pathways of interneurons in the brain and found that they differ in origin from similar cells found in rodents.

“The human cerebral cortex is not only 1,000 times larger than that of a mouse, it also has a subtype of cells that are newer in origin,” said Rakic, senior author of the study. “This has significance for understanding evolution as well as certain human disorders because newly introduced cells in evolution very often have a particular vulnerability to either genetic mutations or to environmental effects.”

The mammalian neocortex contains two major classes of neurons, projection and local circuit neurons. In general, projection neurons contain the excitatory neurotransmitter glutamate, while local circuit neurons, or interneurons, are usually inhibitory and contain the inhibitory neurotransmitter, GABA. However, there are many classes of GABA containing neurons.

The complex function of neocortical circuitry depends on the number and diversity of these interneurons. Interneurons increase in number, complexity and proportion relative to projection neurons during primate evolution and are implicated in a host of neurological disorders.

Rakic and his colleagues labeled neurons in the sections of embryonic brain to trace their origin and migratory pathway, which revealed the existence of two distinct lineages of neocortical interneurons. In this study they provide evidence that most human interneurons, unlike those of other mammals so far examined, come from the proliferative ventricular and subventricular zones of the dorsal forebrain. This makes it possible that distinct lineages of neurons may be differentially affected in genetic and acquired brain diseases.

Co-authors are Kresimir Letinic and Roberto Zoncu, both graduate students at Yale.