Professor of Neurobiology*Lab Homepage: https://fellerlab.squarespace.com/
*Paul Licht Distinguished Professor in Biological Sciences and Member of the Helen Wills Neuroscience Institute
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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 use two-photon imaging, electrophysiology and a variety of anatomical 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. Recently we have focused on a class of neurons called intrinsically phtotsetneive retinal ganglion cells. Second, we study the development and organization of the circuits that mediate direction selectivity in the retina.
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.
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.
Interactions between retinal waves and intrinsically photosensitive retinal ganglion cells
Intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin, are the first photoreceptors that mature in the retina, and they therefore provide the earliest light-driven signals to the brain. We have found that the chemical synaptic circuits that generate waves strongly and dynamically interact with the electrical synaptic circuits that link ipRGCs with other retinal cells. Specifically, we have revealed that acutely blocking retinal waves increases the number of light sensitive neurons. We continue to explore how these circuits interact and what role gap junctions play in the process.
M. El-Quessny, K. Maanum and M. B. Feller. (2020) Visual experience instructs dendrite orientation but is not required for asymmetric wiring of the retinal direction selective circuit, Cell Reports, 31: 107844,
F. Caval-Holme,Y. Zou and M. B. Feller (2019). Gap junction coupling shapes the encoding of light in the developing retina, Current Biology, 2;29(23):4024-4035
A. Tiriac, B. Smith, M. B. Feller (2018). Light prior to eye-opening promotes retinal waves and eye-specific segregation, Neuron, 100(5):1059-1065.
R. D. Morrie and M. B. Feller (2018). A dense starburst plexus is critical for generating direction selectivity, Current Biology, 28(8):1204-1212.
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
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.
A. S. Mauss*, A.L. Vlasits** A. Borst#, M. B. Feller# (2017), “Visual Circuits for Direction Selectivity”, Annual Review Neuroscience, 40:211-230.
R. D. Morrie and M. B. Feller (2016), “Development of synaptic connectivity in the retinal direction selective circuit”, Current Opinion in Neurobiology 40, 45-52.
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.
Photo Credit: Mark Hanson of Mark Joseph Studios
Last Updated 2020-09-10