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Neuroscientists show insulin receptor signaling regulates structure of brain circuits
Date:6/18/2008

eresting, notes Dr. Cline, since "it is required for the incorporation of neurons into brain circuits."

Blocking the Receptor

To test the idea that insulin receptor signaling regulates the formation of brain circuits during development, the Cold Spring Harbor team used two different techniques to block the function of the receptor in neurons located in the visual pathway of tadpoles. One method "knocked down" expression of the receptors genetically, while the other left them in place but prevented them from initiating signaling cascades within the cell.

"Tadpoles are wonderful creatures for such experiments," Dr. Cline explained, "in part because they have translucent bodies, which makes it easy for us to visualize and record what happens to individual neurons as we manipulate the insulin receptors on their surface."

When insulin receptor function was blocked, neurons in the visual pathway connecting the tadpole's retina to a brain region called the tectum responded very poorly to light stimuli. The tectum is the area in which brain cells process incoming visual signals. "We showed that the insulin receptor is critical for the proper operation of this circuit, and also that defects in receptor signaling cause a reduction in the animal's visual responses," Dr. Cline said.

Time-Lapse Images of Dendritic Branching

The team went on to perform other experiments that demonstrated two remarkable facts. One is that insulin receptor signaling correlates with the density of the synapses, or neuron-to-neuron connections, in brain circuits. In more technical terms, they found that insulin receptors maintain synaptic density and that synapse density decreases when insulin receptors are removed or dysfunctional.

The team also secured time-lapse images of dendritic formations, the ethereal, branch-like structures that receive chemical signals sent from one neuron to the next. Again, they found that whe
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Contact: Jim Bono
bono@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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