Carnegie Mellon study identifies impact of neural connections in learning process

studies using viral over-expression systems supports the notion that production of certain AMPA receptors is increased and that they are transported to the synapse during learning. Neuroscientists have always thought implicitly that this phenomenon underlies learning and memory," said Barth. "Our study reveals for the first time in vivo the dynamic activity of these receptors within a single synapse and that these changes result in experience-dependent plasticity during a specific behavioral experience."

Barth's strategy to reveal plasticity in a single synapse involved a two-step approach. First, she used a novel tool she created--a transgenic mouse that couples the green fluorescent protein (GFP) with the gene c-fos, which turns on when nerve cells are activated. Using this method, Barth was able to "light up" clusters of neurons in living brain tissue that were activated during a specific rearing condition --experiencing the world through one whisker. By locating such a cluster of glowing neurons, she could precisely identify the area of the brain involved in processing sensory input from that single whisker. Once these neurons were located, Barth examined how the inputs to these neurons had been modified by experience.

Barth and graduate student Roger Clem, the lead author on the study, found that this change in sensory experience causes a subtle, but very significant, change in AMPA receptor properties at a defined group of synapses in an area of the brain identified by fos-GFP labeling. Barth and Clem achieved this finding by using an electrophysiological technique called patch clamping to detect unique voltage "signatures" that characterize and differentiate in real-time AMPA receptors.

Why would detecting different AMPA receptors be important? Different subtypes of AMPA receptors are highly regulated within a cell. Each AMPA receptor is made from varying combinations of four subunits: GluR1, GluR2, GluR3 or GluR4. The different ratio

Contact: Lauren Ward
Carnegie Mellon University

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