Marla Feller

Professor of Neurobiology
Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute
University of California, Berkeley
(March 28, 2016)

Wiring Up a Circuit to Perform Computations: Development of Direction Selectivity

During development, neurons form circuits with other neurons. These circuits form the basis of brain function. A basic question in neuroscience research, therefore, is how these circuits are formed. How do neurons know to wire with other neurons to perform different functions? Is it based on genetics? In her lecture, Dr. Feller discussed her work examining the wiring of networks in the retina of the eye. Certain neurons in the retina respond to images that move in specific directions. Her lab has found the activity of these neurons is not only determined by genetics but also by activity. They hypothesize that experience during development directs the retinal neurons to respond to certain stimuli and form circuits, and that genetics is only part of the answer.

How are circuits wired up during development to perform specific computations? We address this question in the retina, which comprises multiple circuits that encode different features of the visual scene, culminating in roughly 20 different types of retinal ganglion cells. Direction-selective ganglion cells (DSGCs) respond strongly to an image moving in the preferred direction and weakly to an image moving in the opposite, r null, direction. Direction- selective ganglion cells are critical for driving ocular-motor reflexes that stabilize images on the retina as we move through a visual scene as well as for sensing the movement of objects within the visual scene.

In adult retina, the preferred directions of DSGCs are not randomly distributed but cluster along distinct directions (up, down, left, and right), which we refer to as cardinal axes. The mechanisms that guide the emergence of these cardinal directions and the precise excitatory and inhibitory connectivity that define them are unknown. Work from our lab and others has demonstrated that direction selective responses are detectable at the age of the earliest visual responses, indicating that the retinal circuitry mediating direction that selectivity emerges prior to normal visual experience, and these responses remain after a variety of genetic and pharmacological blockades of synaptic signaling in the early retina. Hence the primary hypothesis has been that direction selective circuits emerge independent of neural activity.

I present recent results from my laboratory that counters this hypothesis and demonstrates that both activity-dependent and independent mechanisms underlie the development of retinal direction selectivity.