Compartmental localization of γ-aminobutyric acid type B receptors in the cholinergic circuitry of the rabbit retina

Abstract

Although many effects of gamma-aminobutyric acid (GABA) on retinal function have been attributed to GABA(A) and GABA(C) receptors, specific retinal functions have also been shown to be mediated by GABA(B) receptors, including facilitation of light-evoked acetylcholine release from the rabbit retina (Neal and Cunningham [1995] J. Physiol. 482:363-372). To explain the results of a rich set of experiments, Neal and Cunningham proposed a model for this facilitation. In this model, GABA(B) receptor-mediated inhibition of glycinergic cells would reduce their own inhibition of cholinergic cells. In turn, muscarinic input from the latter to the glycinergic cells would complete a negative-feedback circuitry. In this study, we have used immunohistochemical techniques to test elements of this model. We report that glycinergic amacrine cells are GABA(B) receptor negative. In contrast, our data reveal the localization of GABA(B) receptors on cholinergic/GABAergic starburst amacrine cells. High-resolution localization of GABA(B) receptors on starburst amacrine cells shows that they are discretely localized to a limited population of its varicosities, the majority of likely synaptic-release sites being devoid of detectable levels of GABA(B) receptors. Finally, we identify a glycinergic cell that is a potential muscarinic receptor-bearing target of GABA(B)-modulated acetylcholine release. This target is the DAPI-3 cell. We propose, based on these data, a modification of the Neal and Cunningham model in which GABA(B) receptors are on starburst, not glycinergic amacrine cells.

Identification of Synaptic Patterns of NMDA Receptor Subtypes Upon Direction-Selective Rabbit Retinal Ganglion Cells

“…The DAPI-3 amacrine cells, which release glycine, co-stratify close to SACs and the dendritic arbors of DS RGCs. 48,49 Although we used ketamine, which is well known as a potent antagonist for blocking NMDA receptors, 50,51 as a general anesthetic in this study, there was no effect in our results where the distributions of NMDA receptor subunits upon the dendritic arbors of the DS RGCs. In order to counter the controversial issue whether ketamine affected our results by blockading the NMDA receptors upon the dendrites of the DS RGCs, we carried out the experiment through the use of a sedated rabbit with only a high dosage of xylazine.…”

Role of acetylcholine in nitric oxide production in the salamander retina

“…They also proposed that the glycinergic cells could be inhibited through metabotropic GABA B receptors. Subsequent work in the rabbit suggested that the effects of GABA are mediated through GABA B autoreceptors on the starburst amacrine cells, which are known to release both ACh and GABA (Zucker et al, 2005). Studies in the frog retina also point to a cholinergic-glycinergic loop in the inner retina, where it is thought to be important in feedback between the ON and OFF channels (Jardon et al, 1989(Jardon et al, , 1992.…”

Cellular Inhibitory Behavior Underlying the Formation of Retinal Direction Selectivity in the Starburst Network

“…are all expressed in a variety of different amacrine cells. Using immunohistochemical labeling Zucker et al [126] have shown that GABA B receptors are expressed on SACs, and a model of a SAC network underlying retinal direction selectivity was proposed by Grzywacz and Zucker [46]. In their model, GABA B autoreceptors on SAC would suppress voltage-gated Ca 2+ channels by activation of secondmessenger cascades, thereby reducing the release of ACh, having a similar effect to GABA A autoreceptors [91].…”

“…As GABA carrier is electrogenic the net direction of GABA flow would depend on the GABA concentration on each side of the SAC membrane. The second mechanism involves tonically mediated inhibition of SACs through GABA B receptors [126] which is light-independent vesicular release that is Ca 2+ -dependent and uptake is by I GABA into the SAC. The third mechanism involves light-dependent via Ca 2+ -dependent vesicular release where both synaptic and extrasynaptic GABA A receptors mediate the negative feedback current I Cl through Cl − channels hyperpolarizing the SAC [120,122].…”

“…However, in the somatofugal direction the cholinergic input is preferentially suppressed by self-inhibitory autoreceptors (i.e., extrasynaptic GABA A receptor [122]) mediating a prolonged negative feedback that prevents an increase in the Ca 2+ -dependent responses in the somatopetal direction [32]. Glossary of various ionic currents found in SACs of the rabbit's retina: I Na -transient inward sodium current [13,23]; I GABATransporter -GABA transporter current [82]; I Ca -calcium inward current (P/Q-type) [23]; I K(Ca) -calcium-activated potassium outward current [8,116,Zhou (personal communication)]; I Cl -chloride inward current mediated by synaptic GABA A receptor [120] and extrasynaptic GABA A receptors [122]; I GABA -tonic inhibitory inward current mediated by extrasynaptic GABA B receptors [126]; I Na−K−Cl -the sodium, potassium, and chloride exchanger current (passive transport) [44]; I K−Cl -potassium and chloride exchanger current (passive transport) [44]; I Na−Ca -sodium and calcium exchanger current (passive transport) [44]; I Ca(ATP) -calcium co-transporter current (ATP) [44]; I K -inward-rectifying potassium current [84] (in the mouse retina); I NaP -prolonged inward sodium current (TTX-resistant) [79] (in the mouse retina) [80].…”