Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-23T19:30:03.962Z Has data issue: false hasContentIssue false
  • English
  • Français

Dissociated GABAergic retinal interneurons exhibit spontaneous increases in intracellular calcium

Published online by Cambridge University Press:  04 October 2006

SALLY I. FIRTH  and
MARLA B. FELLER
SALLY I. FIRTH
Affiliation:
Neurobiology Section, Division of Biological Sciences, University of California at San Diego, San Diego, California Current address of Dr. Sally I. Firth: School of Pharmacy, Steele Building (3), University of Queensland, St Lucia, QLD, 4072, Australia
MARLA B. FELLER
Affiliation:
Neurobiology Section, Division of Biological Sciences, University of California at San Diego, San Diego, California
Get access Rights & Permissions [Opens in a new window]

Abstract

Early in development, before the retina is responsive to light, neurons exhibit spontaneous activity. Recently it was demonstrated that starburst amacrine cells, a unique class of neurons that secretes both GABA and acetylcholine, spontaneously depolarize. Networks comprised of spontaneously active starburst cells initiate correlated bursts of action potentials that propagate across the developing retina with a periodicity on the order minutes. To determine whether other retinal interneurons have similar “pacemaking” properties, we have utilized cultures of dissociated neurons from the rat retina. In the presence of antagonists for fast neurotransmitter receptors, distinct populations of neurons exhibited spontaneous, uncorrelated increases in intracellular calcium concentration. These increases in intracellular calcium concentration were sensitive to tetrodotoxin, indicating they are mediated by spontaneous membrane depolarizations. By combining immunofluorescence and calcium imaging, we found that 44% of spontaneously active neurons were GABAergic and included starburst amacrine cells. Whole cell voltage clamp recordings in the absence of antagonists for fast neurotransmitters revealed that after 7 days in culture, individual retinal neurons receive bursts of GABA-A receptor mediated synaptic input with a periodicity similar to that measured in spontaneously active GABAergic neurons. Low concentrations of GABA-A receptor antagonists did not alter the inter-burst interval despite significant reduction of post-synaptic current amplitude, indicating that pacemaker activity of GABAergic neurons was not influenced by network interactions. Together, these findings indicate that spiking GABAergic interneurons can function as pacemakers in the developing retina.

Keywords

AmacrineCalcium transientsDevelopmentRetinaSpontaneous activity
Type
Research Article
Information
Visual Neuroscience , Volume 23 , Issue 5 , September 2006 , pp. 807 - 814
Copyright
2006 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Akerman, C.J. & Cline, H.T. (2006). Depolarizing GABAergic conductances regulate the balance of excitation to inhibition in the developing retinotectal circuit in vivo. Journal of Neuroscience 26, 5117–5130.Google Scholar
Bahring, R., Standhardt, H., Martelli, E.A., & Grantyn, R. (1994). GABA-activated chloride currents of postnatal mouse retinal ganglion cells are blocked by acetylcholine and acetylcarnitine: How specific are ion channels in immature neurons? European Journal of Neuroscience 6, 1089–1099.Google Scholar
Ben-Ari, Y. (2002). Excitatory actions of gaba during development: The nature of the nurture. National Reviews in Neuroscience 3, 728–739.Google Scholar
Butts, D.A. & Rokhsar, D.S. (2001). The information content of spontaneous retinal waves. Journal of Neuroscience 21, 961–973.Google Scholar
Colicos, M.A., Firth, S.I., Bosze, J., Goldstein, J., & Feller, M.B. (2004). Emergence of realistic retinal networks in culture promoted by the superior colliculus. Developmental Neuroscience 26, 406–416.Google Scholar
Demarque, M., Represa, A., Becq, H., Khalilov, I., Ben-Ari, Y., & Aniksztejn, L. (2002). Paracrine intercellular communication by a Ca2+- and SNARE-independent release of GABA and glutamate prior to synapse formation. Neuron 36, 1051–1061.Google Scholar
Feigenspan, A., Gustincich, S., Bean, B.P., & Raviola, E. (1998). Spontaneous activity of solitary dopaminergic cells of the retina. Journal of Neuroscience 18, 6776–6789.Google Scholar
Feller, M.B., Wellis, D.P., Stellawagen, D., Werblin, F.S., & Shatz, C.J. (1996). Requirement for cholinergic synaptic transmission in the propagation of spontaneous retinal waves. Science 272, 1181–1197.Google Scholar
Firth, S.I., Wang, C.T., & Feller, M.B. (2005). Retinal waves: Mechanisms and function in visual system development. Cell Calcium 37, 425–432.Google Scholar
Fischer, K.F., Lukasiewicz, P.D., & Wong, R.O.L. (1998). Age-dependent and cell-class specific modulation of retinal ganglion cell bursting activity by GABA. Journal of Neuroscience 18, 3767–3778.Google Scholar
Fletcher, E.L. & Kalloniatis, M. (1997). Localisation of amino acid neurotransmitters during postnatal development of the rat retina. The Journal of Comparative Neurology 380, 449–471.Google Scholar
Gonzalez-Islas, C. & Wenner, P. (2006). Spontaneous network activity in the embryonic spinal cord regulates AMPAergic and GABAergic synaptic strength. Neuron 49, 563–575.Google Scholar
Johnson, J., Tian, N., Caywood, M.S., Reimer, R.J., Edwards, R.H., & Copenhagen, D.R. (2003). Vesicular neurotransmitter transporter expression in developing postnatal rodent retina: GABA and glycine precede glutamate. Journal of Neuroscience 23, 518–529.Google Scholar
Jones, B.W., Watt, C.B., Frederick, J.M., Baehr, W., Chen, C.K., Levine, E.M., Milam, A.H., Lavail, M.M., & Marc, R.E. (2003). Retinal remodeling triggered by photoreceptor degenerations. Journal of Comparative Neurology 464, 1–16.Google Scholar
Kasyanov, A.M., Safiulina, V.F., Voronin, L.L., & Cherubini, E. (2004). GABA-mediated giant depolarizing potentials as coincidence detectors for enhancing synaptic efficacy in the developing hippocampus. Proceedings of the National Academy of Science USA 101, 3967–3972. Epub 2004 Mar 3968.Google Scholar
Kim, I.-B., Lee, E.-J., Kim, M.-K., Park, D.-K., & Chun, M.-H. (2000). Choline acetyltransferase-immunoreactive neurons in the developing rat retina. The Journal of Comparative Neurology 427, 604–616.Google Scholar
Kim, I.-B., Park, D.-K., Oh, S.-J., & Chun, M.-H. (1998). Horizontal cells of the rat retina show choline acetyltransferase- and vesicular acetylcholine transporter-like immunoreactivities during early postnatal developmental stages. Neuroscience Letters 253, 83–86.Google Scholar
Koizumi, A., Watanabe, S.-I., & Kaneko, A. (2001). Persistant Na+ current and Ca2+ current boost graded depolarization of rat retinal amacrine cells in culture. Journal of Neurophysiology 86, 1006–1016.Google Scholar
Leitch, E., Coaker, J., Young, C., Mehta, V., & Sernagor, E. (2005). GABA type-A activity controls its own developmental polarity switch in the maturing retina. Journal of Neuroscience 25, 4801–4805.Google Scholar
Manent, J.B., Demarque, M., Jorquera, I., Pellegrino, C., Ben-Ari, Y., Aniksztejn, L., & Represa, A. (2005). A noncanonical release of GABA and glutamate modulates neuronal migration. Journal of Neuroscience 25, 4755–4765.Google Scholar
Mao, B.Q., Hamzei-Sichani, F., Aronov, D., Froemke, R.C., & Yuste, R. (2001). Dynamics of spontaneous activity in neocortical slices. Neuron 32, 883–898.Google Scholar
Marc, R.E., Jones, B.W., Watt, C.B., & Strettoi, E. (2003). Neural remodeling in retinal degeneration. Progress in Retinal and Eye Research 22, 607–655.Google Scholar
Messersmith, E.K. & Redburn, D.A. (1992). gamma-Aminobutyric acid immunoreactivity in multiple cell types of the developing rabbit retina. Visual Neuroscience 8, 201–211.Google Scholar
Meyer-Franke, A., Kaplan, M.R., Pfrieger, F.W., & Barres, B.A. (1995). Characterization of the signalling interactions that promote the survival and growth of developing retinal ganglion cells in culture. Neuron 15, 805–819.Google Scholar
O'Donovan, M.J. (1999). The origin of spontaneous activity in developing networks of vertebrate nervous system. Current Opinion in Neurobiology 9, 94–104.Google Scholar
O'Malley, D., Scandell, J., & Masland, R. (1992). Co-release of acetylcholine and GABA by the startburst amacrine cells. Journal of Neuroscience 12, 1394–1408.Google Scholar
O'Malley, D.M. & Masland, R.H. (1989). Co-release of acetylcholine and gamma-aminobutyric acid by a retinal neuron. Proceedings of the National Academy of Science USA. 86, 3414–3418.Google Scholar
Osborne, N.N., Patel, S., Beaton, D.W., & Neuhoff, V. (1986). GABA neurons in retinas of different species and their postnatal development in situ and in culture in rabbit retina. Cell and Tissue Research. 243, 117–123.Google Scholar
Peng, Y.W., Hao, Y., Petters, R.M., & Wong, F. (2000). Ectopic synaptogenesis in the mammalian retina caused by rod photoreceptor-specific mutations. National Neuroscience 3, 1121–1127.Google Scholar
Protti, D.A., Gerschenfeld, H.M., & Llano, I. (1997). GABAergic and glycinergic IPSCs in ganglion cells of rat retinal slices. Journal of Neuroscience 17, 6075–6085.Google Scholar
Redburn, D.A., Agarwal, S.H., Messersmith, E.K., & Mitchell, C.K. (1992). Development of the glutamate system in rabbit retina. Neurochemical Research 17, 61–66.Google Scholar
Santos, P.F., Carvalho, A.L., Carvalho, A.P., & Duarte, C.B. (1998). Differential acetylcholine and GABA release from cultured chick retina cells. European Journal of Neuroscience 10, 2723–2730.Google Scholar
Sassoe-Pognetto, M. & Wassle, H. (1997). Synaptogenesis in the rat retina: subcellular localization of glycine receptors, GABA(A) receptors, and the anchoring protein gephyrin. Journal of Comparative Neurology 381, 158–174.Google Scholar
Sernagor, E., Young, C., & Eglen, S.J. (2003). Developmental modulation of retinal wave dynamics: shedding light on the GABA saga. Journal of Neuroscience 23, 7621–7629.Google Scholar
Spitzer, N.C., Borodinsky, L.N., & Root, C.M. (2005). Homeostatic activity-dependent paradigm for neurotransmitter specification. Cell Calcium 37, 417–423.Google Scholar
Stellwagen, D., Shatz, C.J., & Feller, M.B. (1999). Dynamics of retinal waves are controlled by cyclic AMP. Neuron 24, 673–685.Google Scholar
Strettoi, E. & Masland, R.H. (1996). The number of unidentified amacrine cells in the mammalian retina. Proceedings of the National Academy of Science, USA 93, 14906–14911.Google Scholar
Syed, M.M., Lee, S., He, S., & Zhou, Z. (2004a). Spontaneous waves in the ventricular zone of developing mammalian retina. Journal of Neurophysiology 91, 1999–2009.Google Scholar
Syed, M.M., Lee, S., Zheng, J., & Zhou, Z.J. (2004b). Stage-dependent dynamics and modulation of spontaneous waves in the developing rabbit retina. The Journal of Physiology 560, 533–549. Epub 2004 Aug 2012.Google Scholar
Tao, H.W. & Poo, M.M. (2005). Activity-dependent matching of excitatory and inhibitory inputs during refinement of visual receptive fields. Neuron 45, 829–836.Google Scholar
Taschenberger, H. & Grantyn, R. (1995). Several types of Ca2+ channels mediate glutamatergic synaptic responses to activation of single Thy-1-immunolabeled rat retinal ganglion neurons. Journal of Neuroscience 15, 2240–2254.Google Scholar
Versaux-Botteri, C., Pochet, R., & Nguyen-Legros, J. (1989). Immunohistochemical localization of GABA-containing neurons during postnatal development of the rat retina. Investigative Ophthalmology & Visual Science 30, 653–659.Google Scholar
Vu, T.Q., Payne, J.A., & Copenhagen, D.R. (2000). Localization and developmental expression patterns of the neuronal K-Cl cotransporter(KCC2) in rat retina. Journal of Neuroscience 20, 1414–1423.Google Scholar
Wong, W.T., Myhr, K.L., Miller, E.D., & Wong, R.O.L. (2000). Developmental changes in the neurotransmitter regulation of correlated spontaneous retinal activity. Journal of Neuroscience 20, 351–360.Google Scholar
Woodin, M.A., Ganguly, K., & Poo, M.M. (2003). Coincident pre- and postsynaptic activity modifies GABAergic synapses by postsynaptic changes in Cl-transporter activity. Neuron 39, 807–820.Google Scholar
Yazulla, S., Studholme, K.M., & Pinto, L.H. (1997). Differences in the retinal GABA system among control, spastic mutant and retinal degeneration mutant mice. Vision Research 37, 3471–3482.Google Scholar
Zhang, L.L., Pathak, H.R., Coulter, D.A., Freed, M.A., & Vardi, N. (2005). Shift of intracellular chloride concentration in ganglion and amacrine cells of developing mouse retina. Journal of Neurophysiology 21, 21.Google Scholar
Zheng, J., Lee, S., & Zhou, Z.J. (2006). A transient network of intrinsically bursting starburst cells underlies the generation of retinal waves. Nature Neuroscience 9, 363–371.Google Scholar
Zheng, J.J., Lee, S., & Zhou, Z.J. (2004). A developmental switch in the excitability and function of the starburst network in the mammalian retina. Neuron 44, 851–864.Google Scholar
Zhou, Z.J. (2001a). A critical role of the strychnine-sensitive glycinergic system in spontaneous retinal waves of the developing rabbit. Journal of Neuroscience 21, 5158–5168Google Scholar
Zhou, Z.J. (2001b). The function of the cholinergic system in the developing mammalian retina. Progress in Brain Research 131, 599–613.Google Scholar
Zhou, Z.J. & Zhao, D. (2000). Coordinated transitions in neurotransmitter systems for the initiation and propagation of spontaneous retinal waves. Journal of Neuroscience 20, 6570–6577.Google Scholar