Professor of Neurobiology*
*and Member of the Helen Wills Neuroscience Institute
We are interested in the mechanisms that guide the assembly of neural circuits during development. We use the retinas as a model system, where we have used a combination of conventional and two-photon imaging, multielectrode recording, electrophysiology and transgenic approaches to address two major questions. First, we study how immature retinal circuits generate retinal waves -- a term used to describe highly patterned spontaneous activity in the immature retina -- and what role this activity plays in the development of the retina and the retina's connections to the central visual system. Second, we study the development and organization of the circuits that mediate direction selectivity in the retina.
Cellular mechanisms underlying retinal waves:
There are several examples throughout the developing vertebrate nervous system, including the retina, spinal cord, hippocampus and neocortex, where immature neural circuits generate activity patterns that are distinct from the functioning adult circuitry. It has been proposed that these transitional circuits provide the "test patterns" necessary for normal development of the adult nervous system. Spontaneous correlated activity in the developing nervous system is robust to perturbations in the circuits that generate it, suggesting that mechanisms exist to ensure that correlated activity is maintained. We are currently exploring the cellular and circuit mechanisms that underlie this maintenance of spontaneous activity. In addition, we are studying the signaling between neurons and glia duirng development.
Development of direction selectivity
How are circuits wired up during development to perform specific computations? We address this question in the retina, which is comprised of multiple circuits that encode different features of the visual scene, culminating in the roughly 15 different types of retinal ganglion cells. Direction-selective ganglion cells (DSGCs) respond strongly to an image moving in the preferred direction and weakly to an image moving in the opposite, or null direction. In the mammalian retina, the directional preference of an On-Off DSGC is caused in part by asymmetric inhibitory inputs: movement in the null direction causes strong inhibition that effectively shunts light-evoked excitatory inputs. Our lab is working on elucidating other mechanisms that contribute to the generation of direction selectivity and how these directional circuits are wired up during development.
J. M. Rosa*, R. Bos*, C. Fortuny, A. Agarwal, D. E. Bergles, J. G. Flannery, G. S. Sack, M. B. Feller (2015), Neuron-glia signaling in developing retina mediated by neurotransmitter spillover, Elife, doi: 10.7554/eLife.09590 (*equal contributions)
R. D. Morrie and M. B. Feller (2015), An asymmetric increase in inhibitory synapse number underlies the development of a direction selective circuit in the retina, Journal of Neuroscience 35(25):9281-6.
A. Firl, J. Ke, L. Zhang, J. H. Singer, and M. B. Feller (2015), Elucidating the role of AII amacrine cells in glutamatergic retinal waves, Journal of Neuroscience, 35(4): 1675-86.
A. L. Vlasits, R. D. Morrie, C. Fortuny, J. G. Flannery, M. B. Feller, and M. Rivlin-Etzion (2014), Retinal adaptation alters excitatory input to starburst amacrine cells and switches their polarity, Neuron, 83(5):1172-84.
L. A. Kirkby and M. B. Feller (2013),"intrinsically phootsensitive ganglion cells contribute to plastiicty in retinal wave circuits", Proceedings of the National Academy of Sciences,110(29):12090-5.
M. Rivlin-Etzion, W. Wei and M. B. Feller (2012), "Visual stimulation reverses the directional preference of direction selective retinal ganglion cells", Neuron, 76(3):518-25.
Wei W, A. M. Hamby, K. Zhou, M. B. Feller (2011), “Development of asymmetric inhibition underlying direction selectivity in the retina,” Nature ; 469 :402-6.
Barkis, W., K. Ford, and M. B. Feller, (2010). “A target-derived, activity-independent signal induces the transition from excitatory to inhibitory GABA signaling in the mouse retina,” Proceedings of the National Academy of Sciences ;107(51):22302-7.
L. A. Kirkby, G. S, Sack, A. Firl and M. B. Feller (2013), “A role for correlated spontaneous activity in the assembly of neural circuits”, Neuron, 4;80(5):1129-44.
Wei, W and M. B. Feller (2011), "Organization and development of direction selective circuits in the retina". Trends in Neuroscience, 34:638-45.
A. Blankenship and M. B. Feller (2010), Mechanisms underlying spontaneous patterned activity in developing neural circuits, Nature Reviews Neuroscience 11 (1): 18-29.
Photo Credit: Mark Hanson of Mark Joseph Studios
Last Updated 2015-08-27