The Light Response of ON Bipolar Neurons Requires Gα_o

Abstract

ON bipolar neurons in retina detect the glutamate released by rods and cones via metabotropic glutamate receptor 6 (mGluR6), whose cascade is unknown. The trimeric G-protein G o might mediate this cascade because it colocalizes with mGluR6. To test this, we studied the retina in mice negative for the ␣ subunit of G o (G␣ o Ϫ/Ϫ). Retinal layering, key cell types, synaptic structure, and mGluR6 expression were all normal, as was the a-wave of the electroretinogram, which represents the rod and cone photocurrents. However, the b-wave of the electroretinogram, both rod-and cone-driven components, was entirely missing. Because the b-wave represents the massed response of ON bipolar cells, its loss in the G␣ o null mouse establishes that the light response of the ON bipolar cell requires G o . This represents the first function to be defined in vivo for the ␣ subunit of the most abundant G-protein of the brain .

Thenob2mouse, a null mutation inCacna1f: Anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses

“…Similar abnormalities also have been noted in mice lacking expression of bassoon (Dick et al, 2003) as well as in mice that lack functional rod or cone photoreceptors (Claes et al, 2004). In comparison, mice with mutations in the postsynaptic proteins mGluR6, nyctalopin or G α0 , do not share these morphological abnormalities (Pardue et al, 2001;Ball et al, 2003;Masu et al, 1995;Tagawa et al, 1999;Dhingra et al, 2000Dhingra et al, , 2002.…”

“…When only synaptic transmission is compromised, the a-wave component, reflecting activity of rod and cone photoreceptors (Lamb, 1996), is spared, while the b-wave, reflecting predominantly rod or cone depolarizing bipolar cell (DBC) activity (Robson & Frishman, 1995, 1998Kofuji et al, 2000;Sharma et al, 2005), is reduced. This "negative" ERG pattern has now been reported in mice with mutations in genes encoding mGluR6 (Masu et al, 1995), nyctalopin (Pardue et al, 1998), the G-protein subunit Gα O1 (Dhingra et al, 2000(Dhingra et al, , 2002, the β 2 subunit of VDCCs (Ball et al, 2002), the presynaptic cytomatrix protein bassoon (Dick et al, 2003), or calcium-binding protein 4 (Haeseleer et al, 2004). The wide variety of proteins essential for normal synaptic transmission is suggestive of the intricacy of the synaptic complex linking photoreceptors and DBCs.…”

Control of late off-center cone bipolar cell differentiation and visual signaling by the homeobox gene Vsx1

“…Although a number of genetic abnormalities of the ON visual pathway have been reported (20,(29)(30)(31)(32)(33)(34), the effect of the loss of Vsx1 function reported here is the initial description of a heritable OFF visual pathway-specific abnormality. Our findings suggest that the mild subclinical reduction in the ERG b͞a-wave ratio observed in humans with dominant VSX1 missense mutations (18) is the result of OFF-CB cell dysfunction that reflects the incomplete terminal differentiation of these cells.…”

G-protein–mediated inhibition of the Trp channel TRPM1 requires the Gβγ dimer

“…The metabotropic receptor mGluR6 preferentially couples to the G o class of G protein, both in bipolar cells (8,9) and expression systems (10,11). Activation of mGluR6 and, correspondingly, Go, results in closure of TRPM1.…”