UC San Diego

Many circuits in the developing nervous system generate spontaneous activity. This phenomenon has been studied extensively in the developing retina. Before vision is possible in the retina, neighboring retinal ganglion cells, the retina's projection neurons, spontaneously fire correlated bursts of action potentials separated by long periods of silence. This bursting activity propagates across the retina in the form of "retinal waves". My overall goal was to elucidate the transient features of the developing retina that are the synaptic basis of retinal waves. In the adult retina, circuitry is organized vertically, such that signals travel from the light- sensitive photoreceptors, through a class of excitatory interneuron known as bipolar cells, to retinal ganglion cells, whence the signal is transmitted to the brain. Hence, in the adult retina, each point in visual space is represented by excitation in a small group of cells, with minimal lateral communication among neighboring groups of cells. In contrast, during development, retinal waves propagate laterally across many degrees of visual space. Using a combination of transgenic mice and physiological recordings from acutely isolated mouse retinas, I tested two hypotheses regarding how activity propagates laterally across the retina during development. First, I tested whether extrasynaptic glutamate provides a source of coupling among neighboring bipolar cells. Second, I tested whether specific neuronal connexins, which are the proteins that form electrical synapses, are involved in wave generation. These experiments will help us to better understand the mechanisms by which cells in the brain form the correct connections during development. The knowledge gained from these experiments may help to explain congenital defects of the visual system and could be used to help reestablish connections in the injured brain