Research Article: New Research | Sensory and Motor Systems Binocular suppression in the macaque lateral geniculate nucleus reveals early competitive interactions between the eyes https://doi.org/10.1523/ENEURO.0364-20.2020 Cite as: eNeuro 2021; 10.1523/ENEURO.0364-20.2020 Received: 20 August 2020 Revised: 6 November 2020 Accepted: 28 November 2020 This Early Release article has been peer-reviewed and accepted, but has not been through the composition and copyediting processes. The final version may differ slightly in style or formatting and will contain links to any extended data. Alerts: Sign up at www.eneuro.org/alerts to receive customized email alerts when the fully formatted version of this article is published. Copyright © 2021 Dougherty et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. 1 Binocular suppression in the macaque lateral geniculate nucleus 2 reveals early competitive interactions between the eyes 3 4 Abbreviated title: Binocular modulation in primate LGN 5 6 7 Kacie Dougherty1,2, Brock M. Carlson1, Michele A. Cox1,3, Jacob A. Westerberg1, Wolf Zinke1, Michael 8 C. Schmid4, Paul R. Martin5, Alexander Maier1 9 10 1Department of Psychology, College of Arts and Science, Vanderbilt Vision Research Center, Center for 11 Integrative and Cognitive Neuroscience, Vanderbilt University, Nashville, TN 37235, USA 12 2Princeton Neuroscience Institute, Princeton University, Princeton, NJ 09540, USA 13 3Department of Brain and Cognitive Sciences, University of Rochester, Rochester, NY 14620, USA 14 4Faculty of Science and Medicine, University of Fribourg, Chemin du Musée 5 CH-1700 Fribourg, 15 Switzerland 16 5Save Sight Institute and Australian Research Council Centre of Excellence for Integrative Brain 17 Function, The University of Sydney, Sydney, New South Wales 2006, Australia. 18 19 KD, MAC, MCS, AM Designed Research; KD, BMC, JAW, WZ Performed research; PRM Contributed 20 unpublished analytic tools; KD, WZ, PRM Analyzed data; KD, AM Wrote the paper 21 22 Correspondence to Kacie Dougherty, PhD. Email: [email protected] 23 24 6 Figures, 0 Tables, 0 Multimedia 25 Abstract: 245 words, Significance Statement: 104 words, Introduction: 750 words, Discussion: 1549 26 words 27 28 Funding: Supported by a research grant from the National Eye Institute (1R01EY027402-03) and 29 National Eye Institute Training Grant (5T32EY007135-23) to JAW and K.D, National Institute of Mental 30 Health Training Grant (5T32MH065214-17) to K.D, and National Eye Institute Training Grant 31 (1F31EY031293-22) to J.A.W. M.C.S. is supported by ERC grant OptoVision 637638. 32 Conflicts of Interest: The authors report no conflicts of interest. 33 34 Acknowledgments: We thank M. Schall, B. Mitchell, L. Daumail, M. Feurtado, C. Jones, K. Shuster, M. 35 Maddox, S. Motorny, P. Henry, D. Richardson, K. Torab, C. Subraveti, M. Johnson, B. Williams and R. 36 Williams for technical advice and assistance. We thank B. Cumming, V. Casagrande, Y. Jiang, and F. 37 Briggs for input and feedback at an early stage of this work. 38 39 40 Abstract 41 The lateral geniculate nucleus (LGN) of the dorsal thalamus is the primary recipient of the two 42 eyes’ outputs. Most LGN neurons are monocular in that they are activated by visual stimulation 43 through only one (dominant) eye. However, there are both intrinsic connections and inputs from 44 binocular structures to the LGN that could provide these neurons with signals originating from 45 the other (non-dominant) eye. Indeed, previous work introducing luminance differences across 46 the eyes or using a single-contrast stimulus showed binocular modulation for single unit activity 47 in anesthetized macaques and multiunit activity in awake macaques. Here, we sought to 48 determine the influence of contrast viewed by both the non-dominant and dominant eyes on LGN 49 single-unit responses in awake macaques. To do this, we adjusted each eye’s signal strength by 50 independently varying the contrast of stimuli presented to the two eyes. Specifically, we 51 recorded LGN single unit spiking activity in two awake macaques while they viewed drifting 52 gratings of varying contrast. We found that LGN neurons of all types (parvo-, magno-, and 53 koniocellular) were significantly suppressed when stimuli were presented at low contrast to the 54 dominant eye and at high contrast to the non-dominant eye. Further, the inputs of the two eyes 55 showed antagonistic interaction, whereby the magnitude of binocular suppression diminished 56 with high contrast in the dominant eye, or low contrast in the non-dominant eye. These results 57 suggest that the LGN represents a site of pre-cortical binocular processing involved in resolving 58 discrepant contrast differences between the eyes. 59 60 61 62 2 63 Significance 64 A fundamental feature of the primate visual system is its binocular arrangement, which affords 65 stereovision and hyperacuity. A consequence of this arrangement is that the two eyes’ views 66 need to be resolved to yield singular vision, which is normally accomplished by fusion or 67 suppression of one of the eye’s inputs. This binocular processing has been shown to occur in 68 cortex, subsequent to thalamic processing. Here, we show that neurons in the lateral geniculate 69 nucleus receiving excitatory retinal input from one eye can be suppressed by high-contrast visual 70 stimulation of the other eye, indicating that the geniculate serves as a pre-cortical site of 71 binocular processing. 72 73 74 75 76 77 78 79 80 81 82 83 3 84 Introduction 85 The lateral geniculate nucleus (LGN) is the main recipient of the outputs of the two eyes 86 in primates. Its anatomical organization raises the question of the role it plays in resolving 87 binocular inputs to support singular vision. In diurnal primates, the LGN comprises distinct 88 layers and virtually all neurons within each layer receive direct inputs from only one eye (Kaas et 89 al., 1972). Neurons within a layer receive input from one eye and neighboring layers contain 90 neurons that receive input from the other eye. Congruent with their inputs, almost all LGN 91 neurons are monocular, exclusively excited by stimulation of one eye. Nevertheless, LGN 92 neurons might interact across layers (Campo-Ortega, Glees, Neuhoff, 1968; Saini and Garey, 93 1981) or receive inputs from structures with binocular neurons (Lund et al., 1975; Hubel and 94 Wiesel, 1968). The effects of these influences could manifest as a difference in magnitude of 95 visual responses under binocular stimulation relative to monocular stimulation. 96 Studies in cats have well-established that spike rates of most LGN neurons are altered by 97 binocular stimulation (Sanderson et al., 1971; Schmielau and Singer, 1977; Xue et al., 1987; 98 Tong et al., 1992; Sengpiel et al., 1995). Binocular modulation also occurs in the primate. Unlike 99 in the cat, related work in macaques has not focused on visual contrast. Instead, previous work 100 on binocular modulation either introduced luminance differences across the eyes (Rodieck and 101 Dreher, 1979; Schroeder et al., 1990) or introduced stimuli at one contrast level (Marrocco and 102 McClurkin, 1979). One reason to address this question in macaques is that cat LGN differs 103 anatomically from primate LGN (reviewed by Dougherty et al., 2018). Assessing binocular 104 modulation in the LGN as a function of visual contrast in both eyes would reveal how 105 interactions between the eyes is influenced by the strength of each eye’s signal. Contrast- 4 106 dependent binocular interactions in the LGN could have implications for known psychophysical 107 phenomena, such as interocular suppression. 108 The primate LGN is composed of three major cell classes—parvocellular (P), 109 magnocellular (M), and koniocellular (K) neurons—with known functional and anatomical 110 distinctions. Known differences in contrast sensitivity among these parallel pathways (Shapley et 111 al., 1981; Derrington and Lennie, 1984; Norton et al., 1988; Lee et al., 1989a; Sclar et al., 1990) 112 as well as their physical distribution could impact whether contrast-dependent binocular 113 interactions occurs for these groups. Based on the studies that assessed general binocular 114 modulation, it remains unclear whether this modulation occurs only for M or both P and M 115 neurons (Marrocco and McClurkin, 1979; Rodieck and Dreher, 1979). Furthermore, whether K 116 neurons, intercalated between different eye-dominant layers, show binocular modulation in 117 macaques is an outstanding question. Recent work in anesthetized marmosets, focusing on K 118 layers, found that about one third of K neurons get excitatory binocular input (Zeater et al., 119 2015), and that most K neurons with excitatory responses to high-contrast stimuli were 120 suppressed by binocular stimulation (Belluccini et al., 2019). A second question is how binocular 121 modulation of single neurons may be impacted by anesthesia, as anesthesia is known to affect 122 binocular processing in this structure (Schroeder et al., 1988). Only one study thus far has 123 considered LGN binocular processing in the awake state (Schroeder et al., 1990). However, these 124 measures were based on population spiking, which could have included spikes from neighboring 125 eye-dominate layers. 126 We sought to determine how visual contrast viewed by both eyes impacts the visual 127 response of LGN neurons receiving direct input from one eye only in awake primates. To do this, 128 we varied the contrast of stimuli shown to the eyes independently to adjust the signal strength 5 129 each eye carries. Two macaques viewed drifting sine-wave gratings presented to one or both 130 eyes while spiking of LGN neurons was recorded with a linear multicontact electrode array.