Temporal Modulation of Scotopic Visual Signals by A17 Amacrine Cells in Mammalian Retina In Vivo

Abstract

We examined function of the feedback pathway from A17 GABAergic amacrine cells to rod bipolar cells (A17 feedback), a critically located inhibitory circuit in the classic rod pathway of the mammalian retina whose role in processing of scotopic visual information is still poorly understood. We show evidence that this A17 feedback has a profound influence on the temporal properties of rod-driven postphotoreceptoral responses (assessed with the scotopic electroretinogram b-wave). Application of a GABAcantagonist prolonged preferentially the decay of the scotopic b-wave. The degree of prolongation increased as the light intensity decreased. Application of selective GABAa antagonists accelerated the kinetics of the scotopic b-wave. This effect was abolished when the GABAc antagonist was coapplied. Selective ablation of A17 cells mimicked the action of the GABAc antagonist. In A17 cell–ablated retinas, the GABAc antagonist was no longer very effective to slow the decay of the scotopic b-wave. Thus the A17 feedback, activated by light stimulation and mediated mainly by the GABAc receptors, makes the scotopic b-wave more transient by accelerating preferentially its decay. The strength of the feedback can be modulated by GABAa receptor–mediated inhibition and by light intensity. Our results also suggest that in the mammalian retina the feedback may be a novel mechanism that contributes postphotoreceptorally to the termination of rod signals, especially those elicited by very dim light stimuli.

BK Channels Mediate Pathway-Specific Modulation of Visual Signals in theIn VivoMouse Retina

“…3C, solid arrows), whereas the initial part of the b-wave was not affected by the mutation. This characteristic alteration of the b-wave in Bk Ϫ/Ϫ mice is in agreement with changes in the b-wave of rabbits following pharmacological ablation of A17s (Dong and Hare, 2003). In the rabbit, lack of A17 feedback resulted in a prolonged trailing edge of the b-wave, whereas its ascending edge was unchanged.…”

Disruption of a Neural Microcircuit in the Rod Pathway of the Mammalian Retina by Diabetes Mellitus

“…GABA C Rs on RBCs are activated by synaptic input from both reciprocal (A17) and nonreciprocal amacrine cells (Hartveit, 1999;Chávez et al, 2006Chávez et al, , 2010Lukasiewicz, 2006, 2011). To distinguish between these two inputs we used 5,7-DHT, a neurotoxin that specifically eliminates input to RBCs from reciprocal A17 amacrines (Dong and Hare, 2003;Chávez et al, 2006), but not from nonreciprocal amacrine cells (Chávez et al, 2010). For AII amacrines from normal animals, adding 5,7-DHT to the bath solution resulted in a significant increase of spEPSC frequency ( Fig.…”

“…There is evidence that these ERG abnormalities are most prominent and consistent under scotopic conditions, suggesting a higher susceptibility of rod pathways (Aung et al, 2013;Pardue et al, 2014). Specifically, reduced activation of GABA C Rs at RBC axon terminals could result in reduced dynamic range of scotopic visual responses (Dong and Hare, 2003;Herrmann et al, 2011) and reduced visual sensitivity (Diamond and Grimes, 2014). In a wider perspective, the current results underscore the importance of bridging the gap between specific molecular pathologies and the resulting functional consequences at the levels of microcircuits, networks, and global function.…”

RETINAL PROCESSING NEAR ABSOLUTE THRESHOLD: From Behavior to Mechanism

“…The connections to the AII and A17 amacrine cells are the best studied. The A17 amacrines (S1/S2 amacrines in rabbit retina) modulate the rod signals by providing inhibitory feedback to rod bipolar synaptic terminals [78,79,80,81,82]. Although the AII amacrines are a requisite component of the rod bipolar pathway, little is known about how single photon responses traverse the rod bipolar-to-AII amacrine synapse.…”