Striking The Right Balance Between Excitation And Inhibition

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Striking The Right Balance Between Excitation And Inhibition

http://www.medicalnewstoday.com/medicalnews.php?newsid=44366

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 excitation 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.