GABA inhibitory feedback from horizontal cells to cones is strongest at night in the dark and suppressed by light.

Abstract

Purpose : GABA_A receptor (GABA_AR) function increases when intracellular cAMP increases (Luscher et al, 2011). In addition, the retinal circadian clock, which activates cone dopamine D₄Rs in the day, increases cAMP in cones at night by not activating D₄Rs (Ribelayga et al, 2002). We therefore studied whether 1) the clock uses D₄Rs to increase cone GABA_AR activity at night compared to day; and 2) horizontal cell (HC) inhibitory feedback to cones is strongest at night in the dark, suppressed by light, and dependent on cone GABA_ARs and D₄Rs.

Methods : Cone responses in intact goldfish retinas to GABA puffed onto their terminals were studied in the day and night during synaptic blockade (20 mM Mg²⁺) and with TPMPA (GABA_CR antagonist).
The effects of artificially polarizing HCs on nearby cones were studied in the day and night in the presence and absence of gabazine (GBZ; GABA_AR antagonist) or spiperone (Spip; D₄R antagonist) (HCs: sharp pipettes; cones: patch pipettes).

Results : Cones responded to GABA puffs at night in the dark and in the day in the dark in the presence of Spip (which increases cAMP in cones) but did not respond in the day in dark or light. GABA responses were slow and sustained (Kaneko, Tachibana, 1986). GBZ increased cone input resistance at night but not in the day.
Preliminary fish HC/cone paired recordings with MFA (gap junction blocker) in Ringer revealed that at night in the dark and in the day with Spip, but not in the day without Spip, depolarizing and hyperpolarizing HCs hyperpolarized and depolarized nearby cpnes, respectively, a sign-inverted effect of HC polarizations on cone voltage that GBZ blocked. Also, following 30 min in the dark at night, mid-mesopic light suppressed the effects of HC polarizations on cones.

Conclusions : The results show that cone GABA_AR function is dependent on D₄R activation and is greater at night in the dark than in the day in the dark or light. Results also suggest that GABA inhibitory feedback from HCs to cones hyperpolarizes cones, decreases their light responses, and reduces their release of glutamate. Because mesopic light suppressed the effects of HC polarizations on cones, HC inhibitory feedback to cones at night does not mediate surround light responses, which are strongest following maintained (30 min) bright illumination and minimal following maintained darkness (Barlow, Levick, 1969; Chaffiol et al., 2017).

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.