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Striking the right balance between excitation and inhibition

Neurons in the brain and spinal cord come in two flavors, excitatory neurons that transmit and amplify signals, and inhibitory neurons that inhibit and refine those signals. Although investigators have long appreciated that these two classes of neurons exist in the central nervous system, little is known about how cells decide to become inhibitory or excitatory during embryonic development. Researchers at the Salk Institute for Biological Studies have now uncovered a pathway that plays a central role in regulating this choice.

That path is described in a study from Martyn Goulding, PhD., an associate professor in the Molecular Neurobiology Laboratory. Goulding, along with co-lead authors, postdoctoral fellow Rumiko Mizuguchi, PhD., and Sonja Kriks, a graduate student at Georg-August University in Goettingen, Germany, analyzed the origins of a group of spinal cord "interneurons," neurons that bridge communications between other neurons.

Many interneurons emerging in the dorsal part of the spinal cord arise from a common progenitor cell. Since mature neurons can be either excitatory or inhibitory, the researchers asked how a single parental progenitor cell could produce both excitatory and inhibitory daughter cells, and how approximately equal numbers of each daughter cell are produced.

In a study published in the June edition of Nature Neuroscience (now available online), the team found that a receptor protein known as Notch, which was already known to regulate maturation of neurons from neural stem cells, has a reciprocal function in precursors of inhibitory and excitatory neurons: cells with high levels of activated Notch became excitatory neurons, while cells with low levels of Notch became inhibitory.

Interestingly, the researchers found that one way Notch combats an inhibitory fate is to turn off another a factor known as Ptf1a, which promotes that fate. Describing the role of Notch as an arbitrator of the choice between excitat
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Source:Salk Institute


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