Gain control by sparse, ultra-slow glycinergic synapses.

In the retina, ON starburst amacrine cells (SACs) play a crucial role in the direction-selective circuit, but the sources of inhibition that shape their response properties remain unclear. Previous studies demonstrate that ∼95% of their inhibitory synapses are GABAergic, yet we find that the light-evoked inhibitory currents measured in SACs are predominantly glycinergic. Glycinergic inhibition is extremely slow, relying on non-canonical glycine receptors containing α4 subunits, and is driven by both the ON and OFF retinal pathways. These attributes enable glycine inputs to summate and effectively control the output gain of SACs, expanding the range over which they compute direction. Serial electron microscopic reconstructions reveal three specific types of ON and OFF narrow-field amacrine cells as the presumptive sources of glycinergic inhibition. Together, these results establish an unexpected role for specific glycinergic amacrine cells in the retinal computation of stimulus direction by SACs.

Functional changes in Tg P23H-1 rat retinal responses: differences between ON and OFF pathway transmission to the superior colliculus.

The morphological consequences of retinal photoreceptor degeneration are well documented. Much less is known about changes in visual function during degeneration and whether central visual structures directly reflect changes in retinal ganglion cell (RGC) function. To address this, we compared changes in visual function of RGCs and cells in the superior colliculus (SC) in transgenic (Tg) P23H-1 rats, a model of retinitis pigmentosa (RP), and wild-type (WT) rats at postnatal days 35-50 (P35-50) and P300. RGCs were classified on the basis of their responses to light: onset (ON), offset (OFF), or both (ON-OFF). The distribution of ON, OFF, and ON-OFF RGCs is similar between WT and P35 Tg P23H-1 rats. By P300, many Tg P23H-1 RGCs are nonresponsive (NR). At this age, there is a sharp decline in ON and ON-OFF RGCs, and the majority that remain are OFF RGCs. Spontaneous rhythmic activity was observed in many RGCs at P300, but only in OFF or NR RGCs. In the SC, WT and P50 Tg P23H-1 responses are similar. At P300, Tg P23H-1 ON SC responses declined but OFF responses increased. We examined postsynaptic glutamate receptor expression located on the bipolar cells (BC), where the ON and OFF pathways arise. At P150, metabotropic glutamate receptor 6 (mGluR6) expression is lower than in WT, consistent with a decrease in ON RGC responses. GluR4 expression, an ionotropic glutamate receptor associated with OFF BCs, appears similar to that in WT. The loss of ON responses in Tg P23H-1 RGCs and in the SC is conserved and related to reduced mGluR6 signaling.