We are interested in how neural activity affects the assembly of neural circuits. 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 spontaneous activity in the immature retina, termed retinal waves, where it has been demonstrated that these correlated action potentials are involved in the organization of downstream visual centers.
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.
Role of retinal waves in the maturation of 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.
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 EJ Chichilnisky'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.
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", Journal of Neuroscience, in press
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.
Hansen, K. A., C. L. Torborg, J. Elstrott,, M. B. Feller, (2005). "The expression and function of Connexin 36 in the developing mouse retina" J Comp Neurol.,12;493(2), 309-20.
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)
Reviews
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. and M. Scanziani (2005). A precritical period for plasticity in visual cortex, Current Opinion in Neurobiology 15(1), 94-100.
Feller, M. B. (1999). Spontaneous Correlated Activity in Developing Neural Circuits, Neuron 22, 653-656.
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