User:Leelindseya/sandbox

[INTRO: Retinal waves are characterized by spontaneous bursts of action potentials propagated by ganglion cells in the developing retina. These waves occur before photoreceptor maturation and before vision can occur. The waves are thought to propagate across neighboring cells in a 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.] - original Lindsey

Retinal waves are spontaneous bursts of action potentials that propagate in a wave-like fashion across the developing retina. These waves occur before photoreceptor 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.

Observation of Waves in Other Systems
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.

Development
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 synapse 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. SACs are thought to be the source of retinal waves because spontaneous depolarizations have been observed without synaptic excitation.

Cholinergic wave activity eventually dies out and the release of glutamate in bipolar cells generates waves. Bipolar cells differentiate later than amacrine and ganglion cells. Prior to bipolar cells forming connections, the inner plexiform layer is characterized by synaptic connections of amacrine cells. The change from cholinergic mediation to glutamatergic mediation occurs when bipolar cells make their first synaptic connections with ganglion cells. Glutamate, the neurotransmitter contained in bipolar cells, generates spontaneous activity in ganglion cells. Waves are still present after bipolar cells make synaptic connection with amacrine and ganglion cells.

Additional activity involved in retinal waves includes the following. In certain species, GABA is seen to play a role in the frequency and duration of the bursts in ganglion cells. It is seen that interactions of cells varies in different test subjects and at different maturity levels, especially the complex interactions mediated by amacrine cells. Activity propagated via gap junctions has not been observed in all test subjects; for example, research has shown that ferret retina ganglion cells are not coupled. Other studies have shown that extracellular excitatory agents such as potassium could be instrumental in wave propagation. Research suggests that synaptic networks of amacrine and ganglion cells are necessary for production of waves. Broadly put, waves are produced and continue over a relatively long developmental period in which new cellular components of the retina and synapses are added. Variation in the mechanisms of retinal waves account for diversity in the connections between cells and maturation of processes in the retina.

Activity Pattern of Waves
Waves are generated at random, but limited spatially due to a period of refractoriness in cells after bursts of action potentials have been produced. After a wave has been propagated in one place, it cannot be propagated in the same place. Wave induced refractory areas last about forty to sixty seconds. Research suggests that every region of the retina is at equal probability of generating and propagating a wave. The refractory period also determines the velocity (distance between wave fronts per unit time) and periodicity (average time interval between wave-induced calcium transients or depolarizations recorded in a particular neuron in the ganglion cell layer) The density of refractory cells corresponds to how fast retinal waves propagate, for instance if there is a low number or density of refractory cells, the velocity of propagation will be high.

Visualization of Waves
Retinal waves are primarily visualized using calcium imaging and multielectrode recordings. Calcium imaging allows analysis of wave pattern over a large area of the retina (more than with multielectrode recording). Imaging as such has allowed researchers to investigate spatiotemporal properties or waves as well as wave mechanism and function in development.