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2002/3C - Abstract

Grant Information

Aging - Network
Synaptic Structure and Function in Down Syndrome
William Mobley, MD, PhD
Stanford University
Department of Neurology and Neurological Sciences
Funding Status
  • Completed
  • $500,000 per year
  • 1/1/2002 to 12/31/2005


2002/3C - Abstract
Brief Summary
"Synaptic Structure and Function in Down Syndrome"

The principal problem faced by people with Down syndrome (DS) is life-long cognitive impairment. Our hypothesis is that cognitive dysfunction in DS is the result of an imbalance of specific genes on human chromosome 21, acting to cause abnormalities in the structure and function of synapses. The synapse is the point of information transfer between neurons. The proper function of synapses is central to the normal operation of neuronal circuits, including those that mediate cognition. Understanding cognitive dysfunction in DS mandates studies of synaptic function.

In studies on a mouse model of DS, we demonstrated marked abnormalities in the structure and function of hippocampal synapses. Because abnormalities in the hippocampus are implicated in cognitive failure in DS, we will study synapses in this brain region. Our work will address the genetic and cellular mechanisms of hippocampal synaptic dysfunction.

The program's objectives will be: 1) to detail the changes in synaptic structure and function that characterize DS, 2) to define the genetic basis for these changes, and 3) to discover how an extra copy of the responsible gene(s) induces abnormal synaptic structure and function. We expect to discover important new insights into brain dysfunction in DS that will guide future attempts at treating cognitive impairment.

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