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Approach sensitivity in the retina processed by a multifunctional neural circuit

Abstract

The detection of approaching objects, such as looming predators, is necessary for survival. Which neurons and circuits mediate this function? We combined genetic labeling of cell types, two-photon microscopy, electrophysiology and theoretical modeling to address this question. We identify an approach-sensitive ganglion cell type in the mouse retina, resolve elements of its afferent neural circuit, and describe how these confer approach sensitivity on the ganglion cell. The circuit's essential building block is a rapid inhibitory pathway: it selectively suppresses responses to non-approaching objects. This rapid inhibitory pathway, which includes AII amacrine cells connected to bipolar cells through electrical synapses, was previously described in the context of night-time vision. In the daytime conditions of our experiments, the same pathway conveys signals in the reverse direction. The dual use of a neural pathway in different physiological conditions illustrates the efficiency with which several functions can be accommodated in a single circuit.

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Figure 1: PV-5 ganglion cells are sensitive to approaching motion.
Figure 2: PV-5 ganglion cells respond to approaching motion even in the absence of dimming.
Figure 3: Response of PV-5 ganglion cells to lateral motion is suppressed by an ON inhibitory signal.
Figure 4: PV-5 ganglion cells receive a rapid inhibitory input required to suppress responses to lateral motion.
Figure 5: PV-6 OFF ganglion cells respond to lateral motion.
Figure 6: The rapid inhibitory pathway is mediated by an electrical synapse. Unless noted, all traces on this figure are from PV-5 cells in Cx36−/− background.
Figure 7: PV-5 cells receive an inhibitory input from AII amacrine cells.
Figure 8: The functional properties of AII amacrine cells are consistent with the rapid inhibitory signal in PV-5 ganglion cells.

References

  1. 1

    Schiff, W., Caviness, J.A. & Gibson, J.J. Persistent fear responses in rhesus monkeys to the optical stimulus of “looming”. Science 136, 982–983 (1962).

    CAS  Article  Google Scholar 

  2. 2

    King, S.M. & Cowey, A. Defensive responses to looming visual stimuli in monkeys with unilateral striate cortex ablation. Neuropsychologia 30, 1017–1024 (1992).

    CAS  Article  Google Scholar 

  3. 3

    Waldeck, R.F. & Gruberg, E.R. Studies on the optic chiasm of the leopard frog. I. Selective loss of visually elicited avoidance behavior after optic chiasm hemisection. Brain Behav. Evol. 46, 84–94 (1995).

    CAS  Article  Google Scholar 

  4. 4

    King, J.G. Jr., Lettvin, J.Y. & Gruberg, E.D. Selective, unilateral, reversible loss of behavioral responses to looming stimuli after injection of tetrodotoxin of cadmium chloride into the frog optic nerve. Brain Res. 841, 20–26 (1999).

    CAS  Article  Google Scholar 

  5. 5

    Ishikane, H., Gangi, M., Honda, S. & Tachibana, M. Synchronized retinal oscillations encode essential information for escape behavior in frogs. Nat. Neurosci. 8, 1087–1095 (2005).

    CAS  Article  Google Scholar 

  6. 6

    Ball, W. & Tronick, E. Infant responses to impending collision: optical and real. Science 171, 818–820 (1971).

    CAS  Article  Google Scholar 

  7. 7

    King, S.M., Dykeman, C., Redgrave, P. & Dean, P. Use of a distracting task to obtain defensive head movements to looming visual stimuli by human adults in a laboratory setting. Perception 21, 245–259 (1992).

    CAS  Article  Google Scholar 

  8. 8

    Hatsopoulos, N., Gabbiani, F. & Laurent, G. Elementary computation of object approach by wide-field visual neuron. Science 270, 1000–1003 (1995).

    CAS  Article  Google Scholar 

  9. 9

    Gabbiani, F., Krapp, H.G. & Laurent, G. Computation of object approach by a wide-field, motion-sensitive neuron. J. Neurosci. 19, 1122–1141 (1999).

    CAS  Article  Google Scholar 

  10. 10

    Gabbiani, F., Cohen, I. & Laurent, G. Time-dependent activation of feed-forward inhibition in a looming-sensitive neuron. J. Neurophysiol. 94, 2150–2161 (2005).

    Article  Google Scholar 

  11. 11

    Sun, H. & Frost, B.J. Computation of different optical variables of looming objects in pigeon nucleus rotundus neurons. Nat. Neurosci. 1, 296–303 (1998).

    CAS  Article  Google Scholar 

  12. 12

    Huberman, A.D. et al. Architecture and activity-mediated refinement of axonal projections from a mosaic of genetically identified retinal ganglion cells. Neuron 59, 425–438 (2008).

    CAS  Article  Google Scholar 

  13. 13

    Kim, I.J., Zhang, Y., Yamagata, M., Meister, M. & Sanes, J.R. Molecular identification of a retinal cell type that responds to upward motion. Nature 452, 478–482 (2008).

    CAS  Article  Google Scholar 

  14. 14

    Haverkamp, S. & Wässle, H. Immunocytochemical analysis of the mouse retina. J. Comp. Neurol. 424, 1–23 (2000).

    CAS  Article  Google Scholar 

  15. 15

    Manookin, M.B., Beaudoin, D.L., Ernst, Z.R., Flagel, L.J. & Demb, J.B. Disinhibition combines with excitation to extend the operating range of the OFF visual pathway in daylight. J. Neurosci. 28, 4136–4150 (2008).

    CAS  Article  Google Scholar 

  16. 16

    Roska, B. & Werblin, F. Vertical interactions across ten parallel, stacked representations in the mammalian retina. Nature 410, 583–587 (2001).

    CAS  Article  Google Scholar 

  17. 17

    Fried, S.I., Münch, T.A. & Werblin, F.S. Mechanisms and circuitry underlying directional selectivity in the retina. Nature 420, 411–414 (2002).

    CAS  Article  Google Scholar 

  18. 18

    Roska, B., Molnar, A. & Werblin, F.S. Parallel processing in retinal ganglion cells: how integration of space-time patterns of excitation and inhibition form the spiking output. J. Neurophysiol. 95, 3810–3822 (2006).

    Article  Google Scholar 

  19. 19

    Slaughter, M.M. & Miller, R.F. 2-Amino-4-phosphonobutyric acid: a new pharmacological tool for retina research. Science 211, 182–185 (1981).

    CAS  Article  Google Scholar 

  20. 20

    Belgum, J.H., Dvorak, D.R., McReynolds, J.S. & Miyachi, E. Push-pull effect of surround illumination on excitatory and inhibitory inputs to mudpuppy retinal ganglion cells. J. Physiol. (Lond.) 388, 233–243 (1987).

    CAS  Article  Google Scholar 

  21. 21

    McGuire, B.A., Stevens, J.K. & Sterling, P. Microcircuitry of beta ganglion cells in cat retina. J. Neurosci. 6, 907–918 (1986).

    CAS  Article  Google Scholar 

  22. 22

    Mills, S.L., O'Brien, J.J., Li, W., O'Brien, J. & Massey, S.C. Rod pathways in the mammalian retina use connexin 36. J. Comp. Neurol. 436, 336–350 (2001).

    CAS  Article  Google Scholar 

  23. 23

    Feigenspan, A., Teubner, B., Willecke, K. & Weiler, R. Expression of neuronal connexin36 in AII amacrine cells of the mammalian retina. J. Neurosci. 21, 230–239 (2001).

    CAS  Article  Google Scholar 

  24. 24

    Massey, S.C. et al. Multiple neuronal connexins in the mammalian retina. Cell Commun. Adhes. 10, 425–430 (2003).

    CAS  Article  Google Scholar 

  25. 25

    Bloomfield, S.A. & Dacheux, R.F. Rod vision: pathways and processing in the mammalian retina. Prog. Retin. Eye Res. 20, 351–384 (2001).

    CAS  Article  Google Scholar 

  26. 26

    Pourcho, R.G. & Goebel, D.J. A combined Golgi and autoradiographic study of (3H)glycine-accumulating amacrine cells in the cat retina. J. Comp. Neurol. 233, 473–480 (1985).

    CAS  Article  Google Scholar 

  27. 27

    Veruki, M.L. & Hartveit, E. Electrical synapses mediate signal transmission in the rod pathway of the mammalian retina. J. Neurosci. 22, 10558–10566 (2002).

    CAS  Article  Google Scholar 

  28. 28

    Geraghty, R.J., Krummenacher, C., Cohen, G.H., Eisenberg, R.J. & Spear, P.G. Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Science 280, 1618–1620 (1998).

    CAS  Article  Google Scholar 

  29. 29

    Cohen, E.D. & Miller, R.F. The network-selective actions of quinoxalines on the neurocircuitry operations of the rabbit retina. Brain Res. 831, 206–228 (1999).

    CAS  Article  Google Scholar 

  30. 30

    Murphy, G.J. & Rieke, F. Signals and noise in an inhibitory interneuron diverge to control activity in nearby retinal ganglion cells. Nat. Neurosci. 11, 318–326 (2008).

    CAS  Article  Google Scholar 

  31. 31

    Xin, D. & Bloomfield, S.A. Comparison of the responses of AII amacrine cells in the dark- and light-adapted rabbit retina. Vis. Neurosci. 16, 653–665 (1999).

    CAS  Article  Google Scholar 

  32. 32

    Rice, D.S. & Curran, T. Disabled-1 is expressed in type AII amacrine cells in the mouse retina. J. Comp. Neurol. 424, 327–338 (2000).

    CAS  Article  Google Scholar 

  33. 33

    Huang, L. et al. G protein subunit G gamma 13 is coexpressed with G alpha o, G beta 3, and G beta 4 in retinal ON bipolar cells. J. Comp. Neurol. 455, 1–10 (2003).

    CAS  Article  Google Scholar 

  34. 34

    Greferath, U., Grunert, U. & Wassle, H. Rod bipolar cells in the mammalian retina show protein kinase C-like immunoreactivity. J. Comp. Neurol. 301, 433–442 (1990).

    CAS  Article  Google Scholar 

  35. 35

    Oyster, C.W. The analysis of image motion by the rabbit retina. J. Physiol. (Lond.) 199, 613–635 (1968).

    CAS  Article  Google Scholar 

  36. 36

    Olveczky, B.P., Baccus, S.A. & Meister, M. Segregation of object and background motion in the retina. Nature 423, 401–408 (2003).

    Article  Google Scholar 

  37. 37

    Franconeri, S.L. & Simons, D.J. Moving and looming stimuli capture attention. Percept. Psychophys. 65, 999–1010 (2003).

    Article  Google Scholar 

  38. 38

    Bradley, D.C. & Goyal, M.S. Velocity computation in the primate visual system. Nat. Rev. Neurosci. 9, 686–695 (2008).

    CAS  Article  Google Scholar 

  39. 39

    Roska, B., Nemeth, E. & Werblin, F.S. Response to change is facilitated by a three-neuron disinhibitory pathway in the tiger salamander retina. J. Neurosci. 18, 3451–3459 (1998).

    CAS  Article  Google Scholar 

  40. 40

    Volgyi, B., Xin, D. & Bloomfield, S.A. Feedback inhibition in the inner plexiform layer underlies the surround-mediated responses of AII amacrine cells in the mammalian retina. J. Physiol. (Lond.) 539, 603–614 (2002).

    CAS  Article  Google Scholar 

  41. 41

    Wässle, H. Parallel processing in the mammalian retina. Nat. Rev. Neurosci. 5, 747–757 (2004).

    Article  Google Scholar 

  42. 42

    Pang, J.J. et al. Relative contributions of rod and cone bipolar cell inputs to AII amacrine cell light responses in the mouse retina. J. Physiol. (Lond.) 580, 397–410 (2007).

    CAS  Article  Google Scholar 

  43. 43

    Hippenmeyer, S. et al. A developmental switch in the response of DRG neurons to ETS transcription factor signaling. PLoS Biol. 3, e159 (2005).

    Article  Google Scholar 

  44. 44

    Buffelli, M. et al. Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition. Nature 424, 430–434 (2003).

    CAS  Article  Google Scholar 

  45. 45

    Metzger, D. & Feil, R. Engineering the mouse genome by site-specific recombination. Curr. Opin. Biotechnol. 10, 470–476 (1999).

    CAS  Article  Google Scholar 

  46. 46

    Deans, M.R., Gibson, J.R., Sellitto, C., Connors, B.W. & Paul, D.L. Synchronous activity of inhibitory networks in neocortex requires electrical synapses containing connexin36. Neuron 31, 477–485 (2001).

    CAS  Article  Google Scholar 

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Acknowledgements

We are grateful to S. Arber (Friedrich Miescher Institute), D. Paul (Harvard Medical School) and J. Sanes (Harvard University) for providing mouse lines and Robert Margolskee (Mount Sinai School of Medicine) for providing the Gγ13 antibody. We are grateful for the technical assistance of S. Djaffer, B. Gross Scherf and Y. Shimada. We thank members of the Roska lab, P. Lagali, P. Caroni, R. Friedrich and A. Lüthi for comments on the manuscript. The study was supported by Friedrich Miescher Institute funds, a US Office of Naval Research Naval International Cooperative Opportunities in Science and Technology program grant, a Marie Curie Excellence Grant, a Human Frontier Science Program Young Investigator grant, a National Centers of Competence in Research in Genetics grant and a European Union HEALTH-F2-223156 grant to B.R., a Marie Curie Postdoctoral Fellowship to T.A.M., the Centre National de la Recherche Scientifique through the Unité Mixte de Recherche 8550 to R.A.d.S.

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T.A.M. performed electrophysiological experiments, designed experiments and model, and wrote manuscript; R.A.S. designed experiments and model and wrote manuscript; S.S. performed immunohistochemistry; T.J.V. performed electrophysiological experiments, G.B.A. performed and designed electrophysiological experiments; and B.R. designed experiments and model and wrote manuscript.

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Correspondence to Botond Roska.

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Münch, T., da Silveira, R., Siegert, S. et al. Approach sensitivity in the retina processed by a multifunctional neural circuit. Nat Neurosci 12, 1308–1316 (2009). https://doi.org/10.1038/nn.2389

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