Development of asymmetric inhibition underlying direction selectivity in the retina

How does a neural circuit get wired up to perform specific computations? The Feller lab recently addressed this question by studying the circuit mediates direction selectivity in the retina (Wei et al, Nature, 2010).

Direction-selective neurons, which respond selectively to motion in one direction, have been characterized in visual circuits across many species. In the retina, it has been postulated that the ability to discern the direction of motion of an object required asymmetric wiring between the retinal neurons. However, the mechanisms that instruct this asymmetric wiring during development were completely unknown.

In a recent study, Dr. Wei Wei, a postdoctoral researcher in the Feller lab, used paired electrophysiological recordings from transgenic mice that express fluorescence proteins in the cells of interest and two photon-targeted patching -- to unambiguously map out the development of these asymmetric inhibitory synapses onto direction-selective neurons. They found that these synapses start symmetric and weak and then, surprisingly, only the synapses made with neurons located on one side of the direction-selective cell strengthen while the synapses made with neurons located on the opposite side remain weak. By teaming up with MCB graduate student Aaron Hamby and MCB undergraduate Kaili Zhou, they demonstrated that this period of asymmetric strengthening occurs during the second postnatal week, all before the animals has any visual experience and in the absence of any apparent anatomical bias. In addition, they showed that directional responses emerge in the presence of muscimol, a potent but reversible blocker of all spontaneous retinal activity, indicating that this asymmetric strengthening of synapses occurs independent of neural activity.

Retinal direction selectivity has a long Berkeley history having been discovered by Barlow and his collaborators who were taking a sabbatical in Minor Hall in the Department of Optometry in the 1960s at the invitation of Gerald Westheimer. They published a series of papers that inspired many subsequent studies by laboratories around the world to understand the organization of the circuit that mediates it.

In a breakthrough, a group in long-time MCB faculty member Frank Werblin's lab determined that direction selectivity depends on asymmetric wiring between inhibitory interneurons and involved ganglion cells (Fried and Werblin, Nature, 2002). Muming Poo, Professor of Neurobiology in MCB and his student Engert (Nature 2002) demonstrated that the wiring up of direction-selective responses in Xenopus optic tectum. (Engert and Poo, Nature, 2002).