Genetic disruption of the on visual pathway affects cortical orientation selectivity and contrast sensitivity in mice

The retina signals stimulus contrast via parallel On and Off pathways and sends the information to higher visual centers. Here we study the role of the On pathway using mice that have null mutations in the On-specific GRM6 receptor in the retina (Pinto LH, Vitaterna MH, Shimomura K, Siepka SM, Balannik V, McDearmon EL, Omura C, Lumayag S, Invergo BM, Brandon M, Glawe B, Cantrell DR, Donald R, Inayat S, Olvera MA, Vessey KA, Kirstan A, McCall MA, Maddox D, Morgans CW, Young B, Pletcher MT, Mullins RF, Troy JB, Takahashi JS. Vis Neurosci 24: 111-123, 2007; Maddox DM, Vessey KA, Yarbrough GL, Invergo BM, Cantrell DR, Inayat S, Balannik V, Hicks WL, Hawes NL, Byers S, Smith RS, Hurd R, Howell D, Gregg RG, Chang B, Naggert JK, Troy JB, Pinto LH, Nishina PM, McCall MA. J Physiol 586: 4409-4424, 2008). In these "nob" mice, single unit recordings in the primary visual cortex (V1) reveal degraded selectivity for orientations due to an increased response at nonpreferred orientations. Contrast sensitivity in the nob mice is reduced with severe deficits at low contrast, consistent with the phenotype of night blindness in human patients with mutations in Grm6. These cortical deficits can be largely explained by reduced input drive and increased response variability seen in nob V1. Interestingly, increased variability is also observed in the superior colliculus of these mice but does not affect its tuning properties. Further, the increased response variability in the nob mice is traced to the retina, a result phenocopied by acute pharmacological blockade of the On pathway in wild-type retina. Together, our results suggest that the On and Off pathways normally interact to increase response reliability in the retina, which in turn propagates to various central visual targets and affects their functional properties.