Department of Molecular & Cell Biology

Home Faculty and Research Faculty by Name Marla Feller

Marla Feller

Associate Professor of Neurobiology*
*and Member of the Helen Wills Neuroscience Institute

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Research Interests

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, 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 visual system.  Second, we study the development of the circuits that mediate direction selectivity in the retina.  

Current Projects

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. In my laboratory, we study 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 active interneurons, chemical and electrical synapses and neuromodulators in these processes.

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 by asymmetric inhibitory inputs: movement in the null direction causes strong inhibition that effectively shunts light-evoked excitatory inputs. The mechanisms that guide the emergence of directional circuits in the retina are unknown.  Direction selective responses are detected at the age of the earliest visual responses, indicating that the retinal circuitry mediating direction selectivity emerge prior to normal visual experience. Hence, direction-selective circuits emerge at a time during development when the retina itself is undergoing a remarkable transformation from intrinsically generated retinal waves to visually evoked responses.  We use a several several recently developed transgenic mouse models that express GFP in different subtypes of DSGCs, to determine the mechanisms that underlie the development of the two essential features of direction-selective circuits – the maturation of null-side specific inhibition and DSGC mosaics.

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.

Selected Publications

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. 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.

Elstrott J. and M. B. Feller (2010), “Direction selective ganglion cells show symmetric participation in retinal waves during development, Journal of Neuroscience, 30(33):11197-201.

Wei W., J. Elstrott, M. B. Feller (2010) Two-photon targeted recording of GFP-expressing neurons for light responses and live cell imaging in the mouse retina, Nature Protocols, 5(7):1347-52

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.

 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.

Review Articles:

A. Blankenship and M. B. Feller (2010), Mechanisms underlying spontaneous patterned activity in developing neural circuits, Nature Reviews Neuroscience 11 (1):  18-29.

Elstrott and M. B. Feller (2009), Development of direction selectivity: a tale of two circuits, Current Opinion in Neurobiology, 19(3), 293-7.

Torborg C. L. and M. B. Feller (2005). Spontaneous patterned retinal activity and the refinement of retinal projections, Progress in Neurobiology76(4):213-235.

Last Updated 2011-02-02