The role of cellular excitability and neurotransmission in functional circuit assembly in the mammalian retina
Final Report Abstract
The retina parses visual information into parallel channels, each highlighting salient features of the scene. The best-studied aspect of such parallel processing is the separation of signals evoked by light increments and decrements, respectively, into ON and OFF channels. This distinction is initiated at the first synapse in the retina. Dendrites of ON bipolar cells invert photoreceptor signals through metabotropic glutamate receptors whereas OFF bipolar cells express ionotropic glutamate receptors and keep the sign of the response. In addition to functional differences, ON and OFF bipolar cells target their axons to different halves of the retina’s inner plexiform layer (IPL). Retinal ganglion cells (RGCs) by co-stratifying their dendrites with bipolar cell axons in the IPL, inherit their response type. The axons of RGCs form the optic nerve and innervate several subcortical targets, including the dorsolateral nucleus of the thalamus (dLGN) preserving, at maturity, the distinction into ON and OFF responsive cells. Interestingly, early in development RGCs distribute their dendrites throughout the depth of the IPL contacting both ON and OFF bipolar cells, before choosing either. Similarly, the axons of ON and OFF RGCs in the beginning converge onto single dLGN cells before separating. We explored how neuronal activity regulates the separation of parallel ON and OFF processing streams in the retina and dLGN. We find that in the retina itself neurotransmission has a remarkably selective role, regulating synapse formation but not elimination, affecting synapse number but not dendritic or axonal patterning and mediating independently the refinement of ON and OFF circuits even where they converge onto the same postsynaptic cell. In a second study, we discovered a previously unknown pattern of spontaneous activity among neighboring RGCs. Cell pairs of the same response sign fire repetitive coincident burst of action potentials, whereas the bursts of opposite sign RGC pairs do not overlap and occur in a fixed sequence ON before OFF. We show that this pattern of RGC activity is restricted to a short period of development coinciding with ON/OFF segregation of RGC axons in the dLGN, and describe the circuit mechanisms that shape it.
Publications
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A precisely timed asynchronous pattern of ON and OFF retinal ganglion cell activity during the propagation of retinal waves. Neuron 2008 Jun 26; 58 (6): 851-8
Kerschensteiner D. & Wong R.O.L.
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Neurotransmission selectively regulates synapse formation in parallel circuits in vivo. Nature 2009 Aug 20, 460 (7258): 1016-20
Kerschensteiner D., Morgan J.L., Parker E.D., Lewis R.M. & Wong R.O.L.
