Is the input to a GABAergic synapse the sole asymmetry in rabbit's retinal directional selectivity?

Smith-Kettlewell Eye Research Institute, San Francisco, CA 94115, USA.
Visual Neuroscience (Impact Factor: 1.68). 01/1997; 14(1):39-54. DOI: 10.1017/S0952523800008749
Source: PubMed

ABSTRACT We examined contrast, direction of motion, and concentration dependencies of the effects of GABAergic and cholinergic antagonists, and anticholinesterases on responses to movement of On-Off directionally selective (DS) ganglion cells of the rabbit's retina. The drugs tested were curare and hexamethonium bromide (cholinergic antagonists), physostigmine (anticholinesterase), and picrotoxin (GABAergic antagonist). They all reduced the cells' directional selectivity, while maintaining their preferred-null axis. However, cholinergic antagonists did not block directional selectivity completely even at saturating concentrations. The failure to eliminate directional selectivity was probably not due to an incomplete blockade of cholinergic receptors. In a extension of a Masland and Ames (1976) experiment, saturating concentrations of antagonists blocked the effects of exogenous acetylcholine or nicotine applied during synaptic blockade. Consequently, a noncholinergic pathway may be sufficient to account for at least some directional selectivity. This putative pathway interacts with the cholinergic pathway before spike generation, since physostigmine eliminated directional selectivity at contrasts lower than those saturating responses. This elimination apparently resulted from cholinergic-induced saturation, since reduction of contrast restored directional selectivity. Under picrotoxin, directional selectivity was lost in 33% of the cells regardless of contrast. However, 47% maintained their preferred direction despite saturating concentrations of picrotoxin, and 20% reversed the preferred and null directions. Therefore, models based solely on a GABAergic implementation of Barlow and Levick's asymmetric-inhibition model or solely on a cholinergic implementation of asymmetric-excitation models are not complete models of directional selectivity in the rabbit. We propose an alternate model for this retinal property.

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Available from: Franklin R Amthor, Aug 20, 2015
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    • "10 ; O ' Malley et al . , 1992 ; Strang et al . , 2007 ) . ACh and GABA are co - secreted from the SACs ( Kosaka et al . , 1988 ; Lee et al . , 2010 ; Masland , 2005 ; O ' Malley et al . , 1992 ; Vaney and Young , 1988 ) . The DS RGCs lose their direction - selectivity when the SACs are eliminated through immunotoxin mediated cell targeting ( Grzywacz et al . , 1997 ; Yoshida et al . , 2001 ) . These results therefore indicate that the SACs play a critical role in direction - selectivity ."
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    ABSTRACT: Direction-selective retinal ganglion cells (DS RGCs) respond strongly to a stimulus that moves in their preferred direction, but respond weakly or do not respond to a stimulus that moves in the opposite or null direction. DS RGCs are sensitive to acetylcholine, and starburst amacrine cells (SACs) make cholinergic synapses on DS RGCs. We studied the distributions of nicotinic acetylcholine receptor (nAChR) α7 and ß2 subunits on the dendritic arbors of DS RGCs to search for anisotropies that contribute to the directional preferences of DS RGCs. The DS RGCs from the retinas of postnatal mice (postnatal day P5, P10, and P15) were injected with Lucifer yellow, and injected cells were identified by their dendritic morphology. The dendrites of the DS RGCs were labeled with antibodies for either the nAChR α7 or ß2 subunit as well as postsynaptic density protein-95 (PSD-95), visualized by confocal microscopy, and reconstructed from high-resolution confocal images. The distribution of nAChR subunits on the dendritic arbors in both the ON and OFF layers of the RGCs revealed an asymmetrical pattern on early postnatal day P5. However, the distributions of nAChR subunits on the dendritic arbors were not asymmetric on P10 and P15. Our results therefore provide anatomical and developmental evidence suggesting that the nAChR α7 and ß2 subunits may involve in the early direction-selectivity formation of DS RGCs in the mouse retina.
    Experimental Eye Research 05/2014; 122. DOI:10.1016/j.exer.2014.02.021 · 3.02 Impact Factor
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    • "The DS responses observed in the presence of GABA A receptor blockers were surprising considering the abundant literature supporting a critical role for inhibition in mediating directional selectivity (Wyatt and Day, 1976; Caldwell et al., 1978; Taylor and Vaney, 2002). Even in previous studies where directionally selective responses were detectable under saturating concentrations of inhibitory blockers, they were relatively mild (Smith et al., 1996; Grzywacz et al., 1997). Because we had performed our initial experiments at relatively slow stimulus speeds, we next tested the effects of varying speed on DSI, in an attempt to reconcile our findings with previous work. "
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    ABSTRACT: In the retina, presynaptic inhibitory mechanisms that shape directionally selective (DS) responses in output ganglion cells are well established. However, the nature of inhibition-independent forms of directional selectivity remains poorly defined. Here, we describe a genetically specified set of ON-OFF DS ganglion cells (DSGCs) that code anterior motion. This entire population of DSGCs exhibits asymmetric dendritic arborizations that orientate toward the preferred direction. We demonstrate that morphological asymmetries along with nonlinear dendritic conductances generate a centrifugal (soma-to-dendrite) preference that does not critically depend upon, but works in parallel with the GABAergic circuitry. We also show that in symmetrical DSGCs, such dendritic DS mechanisms are aligned with, or are in opposition to, the inhibitory DS circuitry in distinct dendritic subfields where they differentially interact to promote or weaken directional preferences. Thus, pre- and postsynaptic DS mechanisms interact uniquely in distinct ganglion cell populations, enabling efficient DS coding under diverse conditions.
    Neuron 08/2011; 71(4):683-94. DOI:10.1016/j.neuron.2011.06.020 · 15.98 Impact Factor
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    • "Numerous studies have implicated both GABAergic and cholinergic inputs from presynaptic starburst amacrine cells as critical to the generation of direction selective responses (reviewed by Taylor & Vaney, 2003; Demb, 2007). It has been posited that an asymmetric release of GABA and possibly acetylcholine from starburst cell dendrites gives rise to a null inhibition or preferred excitation critical to direction selective ganglion cell responses (Barlow & Levick, 1965; Wyatt & Daw, 1975; Fried et al. 2002; Borg-Graham & Grzywacz, 1991; Grzywacz et al. 1997, 1998). Consistent with an inhibitory mechanism, application of the GABA receptor blocker picrotoxin results in the loss of the direction selective responses of DS cells (Caldwell et al. 1978; Kittila & Massey, 1995; Ackert et al. 2006). "
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    ABSTRACT: One unique subtype of retinal ganglion cell is the direction selective (DS) cell, which responds vigorously to stimulus movement in a preferred direction, but weakly to movement in the opposite or null direction. Here we show that the application of the GABA receptor blocker picrotoxin unmasks a robust excitatory OFF response in ON DS ganglion cells. Similar to the characteristic ON response of ON DS cells, the masked OFF response is also direction selective, but its preferred direction is opposite to that of the ON component. Given that the OFF response is unmasked with picrotoxin, its direction selectivity cannot be generated by a GABAergic mechanism. Alternatively, we find that the direction selectivity of the OFF response is blocked by cholinergic drugs, suggesting that acetylcholine release from presynaptic starburst amacrine cells is crucial for its generation. Finally, we find that the OFF response is abolished by application of a gap junction blocker, suggesting that it arises from electrical synapses between ON DS and polyaxonal amacrine cells. Our results suggest a novel role for gap junctions in mixing excitatory ON and OFF signals at the ganglion cell level. We propose that OFF inputs to ON DS cells are normally masked by a GABAergic inhibition, but are unmasked under certain stimulus conditions to mediate optokinetic signals in the brain.
    The Journal of Physiology 09/2009; 587(Pt 18):4481-95. DOI:10.1113/jphysiol.2009.173344 · 4.54 Impact Factor
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