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Striking the right balance between excitation and inhibition

ion and inhibition, Goulding says: "The degree of Notch expression on one neuron tells the sibling cell that it cannot be the same thing. If it is up-regulated in one cell, Notch will be down-regulated in its sibling. "There are thousands of different kinds of neurons in our incredibly complex nervous system, and we don't understand how this diversity comes about," Goulding explains.

Referring to the multiple roles of Notch, not only in controlling the differentiation of neurons but in determining their excitatory/inhibitory activity, he adds: "Given that we now have a detailed description of how Notch signaling provides a switch that controls the choice between two different neuronal fates, we can now look and see if it is used in similar ways elsewhere to make different kinds of neurons."

The neurons in the dorsal spinal cord analyzed by the Goulding lab form a relay station receiving and interpreting sensory signals from the environment and then sending them to the brain. In doing so these neurons evaluate the strength of sensations.

"An example of how the system works is illustrated by what happens when you cut your finger," Goulding explains. "Initially it hurts a lot, but the pain then eases. One of the reasons that this happens is because inhibitory interneurons in the dorsal spinal cord dampen down their excitatory counterparts, thus dialing down the pain."

Since interneurons play such critical roles in transmitting pain signals, it is thought that some chronic forms of pain are due to an imbalance in excitatory and inhibitory signals carried by interneurons. As such, the findings by the Goulding group are likely to be important for devising animal models to study these pain pathways.


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Source:Salk Institute


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