The long-term structure and the various functions of the brain depend on how synapses form in response to other developmental activities. In particular, changes in biochemistry in the fetus affect how receptors take shape and regulate biochemical transmission.

Disruption of activity-dependent changes due to perinatal disease, emotional neglect, or abnormal sensory environments during childhood can lead to lifelong damage to cognitive and sensory capabilities. By investigating the mechanisms that induce normal and abnormal synaptic development, it may be possible to selectively reactivate them, facilitating recovery from adult brain trauma and degeneration as well as diseases rooted in infancy.

In order to understand mechanisms that control synaptic development responsible for higher brain functions in humans, researchers must first detail the mechanisms that govern simpler neural functions in more primitive nervous systems. The McGovern Institute is therefore supporting studies of molecular mechanisms that control synaptic development in the visual pathways of rodents.

Recent studies have shown, for example, that changes in the mouse visual pathway during development affect the N-Methyl-D-aspartate (NMDA) subtype of the glutamate receptor, and mice mutated to lack the NMDA receptor die at birth. The NMDA receptor is important for overall CNS mapping as well as excitotoxic cell death in neurodegenerative diseases because it regulates the transmission of calcium at different stages of development. Further studies on formation of the NMDA receptor subtype and other activity-dependent receptors will provide insight on cognitive functioning throughout the human life cycle. Multidisciplinary studies in this area will combine biochemical and molecular biological approaches, studies of receptor function in brain slices, and dynamic imaging of structural changes in intact animals and in vitro.