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Associate Professor of Neurobiology*
*and Member of the Helen Wills Neuroscience Institute
Cellular mechanisms underlying retinal waves:
We are using a combination of electrophysiology, imaging and transgenic mice to determine the cellular mechanisms that underlie the spontaneous generation of retinal waves. Retinal wave generation has three components: initiation (waves initiate spontaneously roughly once/minute), propagation (waves propagate at a speed of 120 microns/second) and refractoriness. We are testing the role of various circuit components, including the role of spontaneously depolarizing interneurons in the initiation of retinal waves. We are also studying the relative roles of chemical and electrical synapses in wave propagation. Although the developing retina is made up entirely of excitatory connections, individual waves propagate over the retina and with a non-uniform wavefront velocity and stop at well-defined, but shifting boundaries. Our work has shown that these boundaries are due in part to a refractory period - a finite time following activation of an area of the retina during which it cannot participate in a subsequent wave. Our current hypothesis is that oscillations in the levels of the second messenger cAMP determine the refractory period. We are testing this hypothesis using live indicators of cAMP and PKA.
Role of retinal waves in the development of receptive fields of retinal ganglion cells.
Retinal waves are detected during an extended period perinatally - from one week before birth to two weeks after birth in mice. There is a long period during which vision and retinal waves co-exist -- light responses have been recorded at P10 in mice, which is 3-4 days prior to eye-opening. The developmental impact of both spontaneous and evoked retinal activity prior to eye-opening is supported by several studies demonstrating that pharmacological manipulations of spontaneous activity and light-deprivation during this period both alter the refinement of circuits within the retina and retinal projections to visual thalamus. In collaboration with Sasha Sher and Alan Litke's lab at the UC Santa Cruz and EJ Chichilniksy's lab at the Salk Institute, we are using a multielectrode array to explore the interaction between these two sources of correlated activity - vision and retinal waves - to determine their relative role in the establishment of functional visual circuits. In particular, we are studying how direction selectivity , which requires asymmetric wiring of inhibitory circuits, is established during development.
Role of retinal waves in the maturation retinal projection to its primary targets in the CNS.
We have studied the role of retinal waves in the segregation of retinal ganglion cell axons into eye-specific regions within the lateral geniculate nucleus. In binocular animals, retinal activity has been shown to drive the segregation of retinogeniculate synapses from an initially overlapping population of RGC axon terminals from the two eyes into regions that are eye-specific. Similarly, retinal activity is critical for retinotopic refinement of retinal projections to the superior colliculus. Our goal is to determine what aspects of the spontaneous retinal activity are critical for the detailed anatomy of retinogeniculate projections. To address this questions we have identified transgenic mice lines that have altered spontaneous firing patterns and/or altered retinal projections. In addition, we are studying the effects of altered activity on the morphology of individual retinal ganglion cell axons.
Huberman AD*, W. Wei*, J. Elstrott*, B. K. Stafford, M. B. Feller#, B. A. Barres# (2009). "Genetic identification of an On-Off direction selective retinal ganglion cells subtype reveals a layer specific subcortical map of posterior motion," Neuron, 62, 327-34 (*co-first authors; #co-senior authors).
Blankenship, A.G.,, K. Ford, J. Johnson, R. Seal, R. H. Edwards, D. R. Copenhagen, and M. B Feller (2009). "Synaptic and extrasynaptic factors governing glutamatergic retinal waves," Neuron, 62, 230-241.
Elstrott, J., A. Anishchenko,M. Greschner, A. Sher, A. M. Litke, E.J. Chichilnisky, M. B. Feller, (2008). "Direction selectivity in the retina is established independent of visual experience and early patterned activity," Neuron, 58, 499-506.
Wang, C-T, A. Blankenship*, A. Anishchenko*, J. Elstrott, M. Fikhman, S. Nakanishi and M. B. Feller, (2007). "GABA-A receptor-mediated signaling alters the structure of spontaneous activity in the developing retina", J. Neuroscience, 27:9130-40. (*co-second authors).
Dunn, T *, C-T Wang*, M. A. Colicos, M. Zaccolo, L. M. Dipilato, J. Zhang, R. Y. Tsien, M B. Feller, (2006). "Imaging of cAMP levels and PKA activity reveals that retinal waves drive oscillations in second messenger cascades", Journal of Neuroscience, 26(49):12807-12815. (*co-first authors)
Torborg C. L., K. A. Hansen, M. B. Feller, (2005). "High frequency synchronized bursting drives eye-specific segregation of retinogeniculate projections" Nature Neuroscience, 8 (1), 72-8.
McLaughlin, T*. , C. L. Torborg*, M. B. Feller#, D. D. O'Leary# (2003). "Retinotopic map refinement requires spontaneous retinal waves during a brief critical period of development", Neuron 40, 1147-1160. (*co -first authors, #co-senior authors)
Review Articles:
J. Elstrott and M. B. Feller, (2009), Development of direction selectivity: a tale of two circuits, Current Opinion in Neurobiology in press.
Torborg C. L. and M. B. Feller (2005). Spontaneous patterned retinal activity and the refinement of retinal projections, Progress in Neurobiology 76(4):213-235.
Feller, M. B. (1999). Spontaneous Correlated Activity in Developing Neural Circuits, Neuron 22, 653-656.
Last Updated 2009-06-22