Carnegie Mellon scientists will use cellular imaging in laboratory animals to understand how normal brain circuits are formed during development.
There are two competing explanations for how brain cells find the right neighbors to connect up with, to form the neural circuits that enable the brain to function normally. One theory, an “activity dependent” explanation, suggests that there is an initial exuberance of connections, followed by retraction of all connections that are found, by experience, to be inappropriate. The contrasting explanation suggests that, rather than guided by experience, neural connections are guided in a rapid and precise manner by patterns of gene expression. Preliminary results from the Carnegie Mellon researchers’ initial studies favor this latter explanation.
They will differentiate between the two explanations by using time-lapse two-photon laser scanning microscopy in the animals’ visual cortex. The imaging will enable them to see the actions of the same brain cells over time, in combination with physiological imaging techniques that will detect the activity patterns of large groups of neurons. In parallel with these imaging techniques, the investigators will work to determine which molecular patterning cues may be involved in structuring neural circuits. The will identify candidate genes, and then image the consequences to neural connections when these genes are either over-or-under expressed in the laboratory animals.
Significance: This research may identify the fundamental clues underlying brain circuit formation, which would represent a major advance in our understanding of neural development. Clinically, this could lead to development of approaches to prevent and treat disorders of neural development and to therapies to improve recovery from trauma and neurodegenerative diseases that destroy brain connections.