Retinal waves

Retinal waves are spontaneous bursts of action potentials that propagate in a wave-like fashion across the developing retina. These waves occur before rod and cone maturation and before vision can occur. The signals from retinal waves drive the activity in the dorsal lateral geniculate nucleus (dLGN) and the primary visual cortex. The waves are thought to propagate across neighboring cells in random directions determined by periods of refractoriness that follow the initial depolarization. Retinal waves are thought to have properties that define early connectivity of circuits and synapses between cells in the retina. There is still much debate about the exact role of retinal waves; some contend that the waves are instructional in the formation of retinogeniculate pathways, while others argue that the activity is necessary, but not instructional in the formation of retinogeniculate pathways. Retinal waves are spontaneous bursts of action potentials that propagate in a wave-like fashion across the developing retina. These waves occur before rod and cone maturation and before vision can occur. The signals from retinal waves drive the activity in the dorsal lateral geniculate nucleus (dLGN) and the primary visual cortex. The waves are thought to propagate across neighboring cells in random directions determined by periods of refractoriness that follow the initial depolarization. Retinal waves are thought to have properties that define early connectivity of circuits and synapses between cells in the retina. There is still much debate about the exact role of retinal waves; some contend that the waves are instructional in the formation of retinogeniculate pathways, while others argue that the activity is necessary, but not instructional in the formation of retinogeniculate pathways. One of the first scientists to theorize the existence of spontaneous cascades of electrical activity during retinal development was, computational neurobiologist David J. Willshaw. He proposed that adjacent cells generate electrical activity in a wave-like formation through layers of interconnected pre-synaptic and postsynaptic cells. Activity propagating through a close span of pre- and postsynaptic cells is thought to result in strong electrical activity in comparison to pre- and postsynaptic cells that are farther apart, which results in weaker activity. Willshaw thought this difference in firing strength and location of cells was responsible for determining the activities boundaries. The lateral movement of firing from neighboring cell to neighboring cell, starting in one random area of cells and moving throughout both the pre- and postsynaptic layers, is thought to be responsible for the formation of the retinotopic map. To simulate the cascade of electrical activity, Willshaw wrote a computer program to demonstrate the movement of electrical activity between pre- and postsynaptic cell layers. What Willshaw called spontaneous patterned electrical activity is today referred to as retinal waves. From this purely theoretical concept, Italian scientists Lucia Galli and Lamberto Maffei used animal models to observe electrical activity in ganglion cells of the retina. Before Galli and Maffei, retinal ganglion cell activity had never been recorded during prenatal development. To study ganglion activity, Galli and Maffei used premature rat retinas, between embryonic day 17 and 21, to record electrical activity. Several isolated, single cells were used for this study. The recordings showed cell activity was catalyzed from ganglion cells. Galli and Maffei speculated that the electrical activity seen in the retinal ganglion cells may be responsible for the formation of retinal synaptic connections and for the projections of retinal ganglion cells to the superior colliculus and LGN. As the idea of retinal waves became established, neurobiologist Carla Shatz used calcium imaging and microelectrode recording to visualize the movement of action potentials in a wave-like formation. For more information on calcium imaging and microelectrode recording, see section below. The calcium imaging showed ganglion cells initiating the formation of retinal waves, along with adjacent amacrine cells, which take part in the movement of the electrical activity. Microelectrode recordings were also thought to show LGN neurons being driven by the wave-like formation of electrical activity across neighboring retinal ganglion cells. From these results, it was suggested that the waves of electrical activity were responsible for driving the pattern of spatiotemporal activity and also playing a role in the formation of the visual system during prenatal development. Rachel Wong is another researcher involved in the study of retinal waves. Wong speculated that electrical activity, within the retina, is involved in the organization of retinal projections during prenatal development. More specifically, the electrical activity may be responsible for the segregation and organization of the dLGN. Wong also speculated that specific parts of the visual system, such as the ocular dominance columns, require some form of electrical activity in order to develop completely. She also believed being able to figure out the signals encoded by retinal waves, may allow scientists to better understand how retinal waves play a role in retinal development. Some of the most recent research being conducted is attempting to better understand the encoded signals of retinal waves during development. According to research conducted by Evelyne Sernagor, it is thought that retinal waves are not just necessary for their spontaneous electrical activity but are also responsible for encoding information to be used in the formation of spatiotemporal patterns allowing retinal pathways to become more refined. Using turtles to test this concept, Sernagor used calcium imaging to look at the change in retinal waves during various stages of retinal development. From the study, at the very first stages of development, retinal waves fire quickly and repeatedly, causing what is thought to be a large wave of action potentials across the retina. However, as the turtle nears completion of development, the retinal waves gradually stop spreading and instead become immobile clumps of retinal ganglion cells. This is thought to be a result of GABA changing from excitatory to inhibitory during continual retinal development. Whether the change in retinal wave formation during development is unique to turtles, is still largely unknown. Spontaneous generation and propagation of waves is seen elsewhere in developing circuits. Similar synchronized spontaneous activity early in development has been seen in neurons of the hippocampus, spinal cord, and auditory nuclei.Patterned activity shaping neuronal connections and control of synaptic efficiency in multiple systems including the retina are important for understanding interaction between presynaptic and postsynaptic cells that create precise connections essential to the function of the nervous system. During development, Communication via synapse is important between amacrine cells and other retinal interneurons and ganglion cells which act as a substrate for retinal waves.There are three stages of development that characterize activity of retinal waves in mammals. Before birth, waves are mediated by non-synaptic currents, waves during the period from birth until ten days after birth are mediated by the neurotransmitter acetylcholine acting on nicotinic acetylcholine receptors, waves during the third period from ten days after birth to two weeks later are mediated by ionotropic glutamate receptors. Chemical synapses during the cholinergic wave period involves the starburst amacrine cells (SACs) releasing acetylcholine onto other SACs, which propagates waves. During this period, cholinergic wave production exceeds wave production via gap junctions, of which the signals are quite reduced. This signaling happens before bipolar cells form connections in the inner plexiform layer. SACs are thought to be the source of retinal waves because spontaneous depolarizations have been observed without synaptic excitation.