Interneuron Circuits Tune Inhibition in Retinal Bipolar Cells

Abstract

While connections between inhibitory interneurons are common circuit elements, it has been difficult to define their signal processing roles because of the inability to activate these circuits using natural stimuli. We overcame this limitation by studying connections between inhibitory amacrine cells in the retina. These interneurons form spatially extensive inhibitory networks that shape signaling between bipolar cell relay neurons to ganglion cell output neurons. We investigated how amacrine cell networks modulate these retinal signals by selectively activating the networks with spatially defined light stimuli. The roles of amacrine cell networks were assessed by recording their inhibitory synaptic outputs in bipolar cells that suppress bipolar cell output to ganglion cells. When the amacrine cell network was activated by large light stimuli, the inhibitory connections between amacrine cells unexpectedly depressed bipolar cell inhibition. Bipolar cell inhibition elicited by smaller light stimuli or electrically activated feedback inhibition was not suppressed because these stimuli did not activate the connections between amacrine cells. Thus the activation of amacrine cell circuits with large light stimuli can shape the spatial sensitivity of the retina by limiting the spatial extent of bipolar cell inhibition. Because inner retinal inhibition contributes to ganglion cell surround inhibition, in part, by controlling input from bipolar cells, these connections may refine the spatial properties of the retinal output. This functional role of interneuron connections may be repeated throughout the CNS.

Temporal properties of dual-peak responses of mouse retinal ganglion cells and effects of inhibitory pathways

“…Besides, the second peak might be generated by a more complex amacrine cell network (Fig. 8b), which may include the ''serial inhibitory'' connections (Zhang et al 1997;Roska et al 1998;Eggers and Lukasiewicz 2010).…”

Inputs Underlying the ON–OFF Light Responses of Type 2 Wide-Field Amacrine Cells in TH::GFP Mice

“…Amacrine cells receive inputs from bipolar cells, other amacrine cells, and/or ganglion cells. Amacrine cell outputs include feedback inhibition to bipolar cells (Flores-Herr et al, 2001;Molnar and Werblin, 2007), feedforward inhibition to ganglion cells (Cook and McReynolds, 1998;Roska and Werblin, 2001), and (serial) inhibition to other amacrine cells (Hsueh et al, 2008;Eggers and Lukasiewicz, 2010).…”

Glycine transporter 1 modulates GABA release from amacrine cells by controlling occupancy of coagonist binding site of NMDA receptors

“…In other words, under our experimental conditions, those GABAergic ACs that form reciprocal inhibitory synapses with the Mb terminals do not seem to receive active glycinergic inhibition. Note that GABA A receptor blocker SR95531 can actually increase feedback to Mbs , indicating that GABAergic inputs to ACs via GABA A receptors (Watanabe et al 2000) inhibit GABA release onto Mb terminals via serial inhibitory synapses (Marc and Liu 2000), similar to other vertebrate retinas (Eggers and Lukasiewicz 2010;Zhang et al 1997).…”