Skip to main content Accessibility help

CaV3.2 KO mice have altered retinal waves but normal direction selectivity

  • AARON M. HAMBY (a1), JULIANA M. ROSA (a1), CHING-HSIU HSU (a1) and MARLA B. FELLER (a1) (a2)


Early in development, before the onset of vision, the retina establishes direction-selective responses. During this time period, the retina spontaneously generates bursts of action potentials that propagate across its extent. The precise spatial and temporal properties of these “retinal waves” have been implicated in the formation of retinal projections to the brain. However, their role in the development of direction selective circuits within the retina has not yet been determined. We addressed this issue by combining multielectrode array and cell-attached recordings to examine mice that lack the CaV3.2 subunit of T-type Ca2+ channels (CaV3.2 KO) because these mice exhibit disrupted waves during the period that direction selective circuits are established. We found that the spontaneous activity of these mice displays wave-associated bursts of action potentials that are altered from that of control mice: the frequency of these bursts is significantly decreased and the firing rate within each burst is reduced. Moreover, the projection patterns of the retina demonstrate decreased eye-specific segregation in the dorsal lateral geniculate nucleus (dLGN). However, after eye-opening, the direction selective responses of CaV3.2 KO direction selective ganglion cells (DSGCs) are indistinguishable from those of wild-type DSGCs. Our data indicate that although the temporal properties of the action potential bursts associated with retinal waves are important for activity-dependent refining of retinal projections to central targets, they are not critical for establishing direction selectivity in the retina.


Corresponding author

*Address correspondence to: Marla B. Feller, 142 Life Sciences Additions MSC 3200, University of California at Berkeley, Berkeley, CA 94720-3200. E-mail:


Hide All
Akrouh, A. & Kerschensteiner, D. (2013). Intersecting circuits generate precisely patterned retinal waves. Neuron 79, 322334.
Barlow, H.B. & Hill, R.M. (1963). Selective sensitivity to direction of movement in ganglion cells of the rabbit retina. Science 139, 412414.
Blankenship, A.G. & Feller, M.B. (2010). Mechanisms underlying spontaneous patterned activity in developing neural circuits. Nature Reviews Neuroscience 11, 1829.
Blankenship, A.G., Hamby, A.M., Firl, A., Vyas, S., Maxeiner, S., Willecke, K. & Feller, M.B. (2011). The role of neuronal connexins 36 and 45 in shaping spontaneous firing patterns in the developing retina. The Journal of Neuroscience 31, 999810008.
Borst, A. & Euler, T. (2011). Seeing things in motion: Models, circuits, and mechanisms. Neuron 71, 974994.
Butts, D.A. (2002). Retinal waves: Implications for synaptic learning rules during development. Neuroscientist 8, 243253.
Cain, S.M. & Snutch, T.P. (2013). T-type calcium channels in burst-firing, network synchrony, and epilepsy. Biochimica et Biophysica Acta 1828, 15721578.
Chan, Y-C. & Chiao, C-C. (2008). Effect of visual experience on the maturation of ON-OFF direction selective ganglion cells in the rabbit retina. Vision Research 48, 24662475.
Chan, Y-C. & Chiao, C-C. (2013). The distribution of the preferred directions of the ON-OFF direction selective ganglion cells in the rabbit retina requires refinement after eye opening. Physiological Reports 1, e00013.
Chen, C-C., Lamping, K.G., Nuno, D.W., Barresi, R., Prouty, S.J., Lavoie, J.L., Cribbs, L.L., England, S.K., Sigmund, C.D., Weiss, R.M., Williamson, R.A., Hill, J.A. & Campbell, K.P. (2003). Abnormal coronary function in mice deficient in alpha1H T-type Ca2+ channels. Science 302, 14161418.
Chen, H., Liu, X. & Tian, N. (2014). Subtype-dependent postnatal development of direction- and orientation-selective retinal ganglion cells in mice. Journal of Neurophysiology 112, 20922101.
Chen, M., Weng, S., Deng, Q., Xu, Z. & He, S. (2009). Physiological properties of direction-selective ganglion cells in early postnatal and adult mouse retina. The Journal of Physiology 587, 819828.
Cueni, L., Canepari, M., Adelman, J.P. & Lüthi, A. (2009). Ca(2+) signaling by T-type Ca(2+) channels in neurons. Pflugers Archiv: European Journal of Physiology 457, 11611172.
Cui, J., Ivanova, E., Qi, L. & Pan, Z.H. (2012). Expression of CaV3.2 T-type Ca²⁺ channels in a subpopulation of retinal type-3 cone bipolar cells. Neuroscience 224, 6369.
Elstrott, J. & Feller, M.B. (2010). Direction-selective ganglion cells show symmetric participation in retinal waves during development. The Journal of Neuroscience 30, 1119711201.
Elstrott, J., Anishchenko, A., Greschner, M., Sher, A., Litke, A.M., Chichilnisky, E.J. & Feller, M.B. (2008). Direction selectivity in the retina is established independent of visual experience and cholinergic retinal waves. Neuron 58, 499506.
Firl, A., Sack, G.S., Newman, Z.L., Tani, H. & Feller, M.B. (2013). Extrasynaptic glutamate and inhibitory neurotransmission modulate ganglion cell participation during glutamatergic retinal waves. Journal of Neurophysiology 109, 19691978.
Ford, K.J. & Feller, M.B. (2012). Assembly and disassembly of a retinal cholinergic network. Visual Neuroscience 29, 6171.
Ford, K.J., Félix, A.L. & Feller, M.B. (2012). Cellular mechanisms underlying spatiotemporal features of cholinergic retinal waves. The Journal of Neuroscience 32, 850863.
Frenkel, M.Y. & Bear, M.F. (2004). How monocular deprivation shifts ocular dominance in visual cortex of young mice. Neuron 44, 917923.
Galli, L. & Maffei, L. (1988). Spontaneous impulse activity of rat retinal ganglion cells in prenatal life. Science 242, 9091.
Guido, W. (2008). Refinement of the retinogeniculate pathway. The Journal of Physiology 586, 43574362.
Hu, C., Bi, A. & Pan, Z-H. (2009). Differential expression of three T-type calcium channels in retinal bipolar cells in rats. Visual Neuroscience 26, 177187.
Huberman, A.D., Feller, M.B. & Chapman, B. (2008). Mechanisms underlying development of visual maps and receptive fields. Annual Review of Neuroscience 31, 479509.
Huberman, A.D., Wei, W., Elstrott, J., Stafford, B.K., Feller, M.B. & Barres, B.A. (2009). Genetic identification of an On-Off direction-selective retinal ganglion cell subtype reveals a layer-specific subcortical map of posterior motion. Neuron 62, 327334.
Kay, J.N., De la Huerta, I., Kim, I.J., Zhang, Y., Yamagata, M., Chu, M.W., Meister, M. & Sanes, J.R. (2011). Retinal ganglion cells with distinct directional preferences differ in molecular identity, structure, and central projections. The Journal of Neuroscience 31, 77537762.
Kerschensteiner, D., Morgan, J.L., Parker, E.D., Lewis, R.M. & Wong, R.O.L. (2009). Neurotransmission selectively regulates synapse formation in parallel circuits in vivo. Nature 460, 10161020.
Kirkby, L.A., Sack, G.S., Firl, A. & Feller, M.B. (2013). A role for correlated spontaneous activity in the assembly of neural circuits. Neuron 80, 11291144.
Lee, S.C., Hayashida, Y. & Ishida, A.T. (2003). Availability of low-threshold Ca2+ current in retinal ganglion cells. Journal of Neurophysiology 90, 38883901.
Ma, Y.P. & Pan, Z.H. (2003). Spontaneous regenerative activity in mammalian retinal bipolar cells: Roles of multiple subtypes of voltage-dependent Ca2+ channels. Visual Neuroscience 20, 131139.
Maccione, A., Hennig, M.H., Gandolfo, M., Muthmann, O., van Coppenhagen, J., Eglen, S.J., Berdondini, L. & Sernagor, E. (2014). Following the ontogeny of retinal waves: Pan-retinal recordings of population dynamics in the neonatal mouse. The Journal of Physiology 592, 15451563.
Marshel, J.H., Kaye, A.P., Nauhaus, I. & Callaway, E.M. (2012). Anterior-posterior direction opponency in the superficial mouse lateral geniculate nucleus. Neuron 76, 713720.
Meister, M., Wong, R.O., Baylor, D.A. & Shatz, C.J. (1991). Synchronous bursts of action potentials in ganglion cells of the developing mammalian retina. Science 252, 939943.
Pan, Z.H., Hu, H.J., Perring, P. & Andrade, R. (2001). T-type Ca(2+) channels mediate neurotransmitter release in retinal bipolar cells. Neuron 32, 8998.
Perez-Reyes, E. (2003). Molecular physiology of low-voltage-activated t-type calcium channels. Physiological Reviews 83, 117161.
Piscopo, D.M., El-Danaf, R.N., Huberman, A.D. & Niell, C.M. (2013). Diverse visual features encoded in mouse lateral geniculate nucleus. The Journal of Neuroscience 33, 46424656.
Puthussery, T., Percival, K.A., Venkataramani, S., Gayet-Primo, J., Grünert, U. & Taylor, W.R. (2014). Kainate receptors mediate synaptic input to transient and sustained OFF visual pathways in primate retina. The Journal of Neuroscience 34, 76117621.
Rivlin-Etzion, M., Zhou, K., Wei, W., Elstrott, J., Nguyen, P.L., Barres, B.A., Huberman, A.D. & Feller, M.B. (2011). Transgenic mice reveal unexpected diversity of on-off direction-selective retinal ganglion cell subtypes and brain structures involved in motion processing. The Journal of Neuroscience 31, 87608769.
Sargoy, A., Sun, X., Barnes, S. & Brecha, N.C. (2014). Differential calcium signaling mediated by voltage-gated calcium channels in rat retinal ganglion cells and their unmyelinated axons. PLoS ONE 9, e84507.
Sernagor, E., Eglen, S.J. & Wong, R.O. (2001). Development of retinal ganglion cell structure and function. Progress in Retinal and Eye Research 20, 139174.
Singer, J.H. & Diamond, J.S. (2003). Sustained Ca2+ entry elicits transient postsynaptic currents at a retinal ribbon synapse. The Journal of Neuroscience 23, 1092310933.
Sivyer, B., van Wyk, M., Vaney, D.I. & Taylor, W.R. (2010). Synaptic inputs and timing underlying the velocity tuning of direction-selective ganglion cells in rabbit retina. The Journal of Physiology 588, 32433253.
Stafford, B.K., Sher, A., Litke, A.M. & Feldheim, D.A. (2009). Spatial-temporal patterns of retinal waves underlying activity-dependent refinement of retinofugal projections. Neuron 64, 200.
Sun, L., Han, X. & He, S. (2011). Direction-selective circuitry in rat retina develops independently of GABAergic, cholinergic and action potential activity. PLoS ONE 6, e19477.
Tian, N. (2008). Synaptic activity, visual experience and the maturation of retinal synaptic circuitry. The Journal of Physiology 586, 43474355.
Torborg, C.L. & Feller, M.B. (2004). Unbiased analysis of bulk axonal segregation patterns. Journal of Neuroscience Methods 135, 1726.
Torborg, C.L., Hansen, K.A. & Feller, M.B. (2005). High frequency, synchronized bursting drives eye-specific segregation of retinogeniculate projections. Nature Neuroscience 8, 7278Epub2004Dec19.
Turrigiano, G.G. & Nelson, S.B. (2004). Homeostatic plasticity in the developing nervous system. Nature Reviews Neuroscience 5, 97107.
Wei, W. & Feller, M.B. (2011). Organization and development of direction-selective circuits in the retina. Trends in Neurosciences 34, 638645.
Wei, W., Elstrott, J. & Feller, M.B. (2010). Two-photon targeted recording of GFP-expressing neurons for light responses and live-cell imaging in the mouse retina. Nature Protocols 5, 13471352.
Wei, W., Hamby, A.M., Zhou, K. & Feller, M.B. (2011). Development of asymmetric inhibition underlying direction selectivity in the retina. Nature 469, 402406Epub2010Dec5.
Wong, R.O.L. (1999). Retinal waves and visual system development. Annual Review of Neuroscience 22, 2947.
Xu, H-P., Chen, H., Ding, Q., Xie, Z-H., Chen, L., Diao, L., Wang, P., Gan, L., Crair, M.C. & Tian, N. (2010). The immune protein CD3zeta is required for normal development of neural circuits in the retina. Neuron 65, 503515.
Xu, H.P., Furman, M., Mineur, Y.S., Chen, H., King, S.L., Zenisek, D., Zhou, Z.J., Butts, D.A., Tian, N., Picciotto, M.R. & Crair, M.C. (2011). An instructive role for patterned spontaneous retinal activity in mouse visual map development. Neuron 70, 11151127.
Yonehara, K., Balint, K., Noda, M., Nagel, G., Bamberg, E. & Roska, B. (2011). Spatially asymmetric reorganization of inhibition establishes a motion-sensitive circuit. Nature 469, 407410.
Zhou, Z.J. (1998). Direct participation of starburst amacrine cells in spontaneous rhythmic activities in the developing mammalian retina. The Journal of Neuroscience 18, 41554165.


CaV3.2 KO mice have altered retinal waves but normal direction selectivity

  • AARON M. HAMBY (a1), JULIANA M. ROSA (a1), CHING-HSIU HSU (a1) and MARLA B. FELLER (a1) (a2)


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed