Cation–chloride cotransporters mediate neural computation in the retina

Gavrikov, K.E.; Dmitriev, Andrey V.; Keyser, Kent T.; Mangel, Stuart C.

doi:10.1073/pnas.2637041100

Cited by 72 publications

(98 citation statements)

References 36 publications

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“…In contrast, GABA release from the distal SAC dendrite will be minimal when the dendrite is hyperpolarized by light stimuli that move in the centripetal direction. The directional release of GABA from SAC dendrites that point in the null direction of DS ganglion cells and that are located on the null side of the ganglion cells will thus confer null direction inhibition on DS ganglion cells (5,6).…”

Section: Discussionmentioning

confidence: 99%

“…Retinal eyecups were obtained after deep general (urethane, 1.5 g/kg, i.p.) and local intraorbital (2% Xylocaine) anesthesia of New Zealand white rabbits (2.5 kg) (5). Animal care and use followed all federal and institutional guidelines.…”

Section: Methodsmentioning

confidence: 99%

“…Starburst amacrine cells (SACs), interneurons presynaptic to the DS ganglion cells, are an essential component of the mechanism that generates direction selectivity in the retina because selective elimination of this interneuron eliminates the directional light responses of DS ganglion cells (2,3). Moreover, SAC dendrites generate DS light responses (4,5), providing DS input to DS ganglion cells (5,6). They hyperpolarize to stimuli that move centripetally from the periphery to their proximal dendrites but depolarize to stimuli that move centrifugally from their proximal dendrites to the periphery (5).…”

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Dendritic compartmentalization of chloride cotransporters underlies directional responses of starburst amacrine cells in retina

Gavrikov

Nilson

Dmitriev

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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119

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The mechanisms in the retina that generate light responses selective for the direction of image motion remain unresolved. Recent evidence indicates that directionally selective light responses occur first in the retina in the dendrites of an interneuron, i.e., the starburst amacrine cell, and that these responses are highly sensitive to the activity of Na-K-2Cl (NKCC) and K-Cl (KCC), two types of chloride cotransporter that determine whether the neurotransmitter GABA depolarizes or hyperpolarizes neurons, respectively. We show here that selective blockade of the NKCC2 and KCC2 cotransporters located on starburst dendrites consistently hyperpolarized and depolarized the starburst cells, respectively, and greatly reduced or eliminated their directionally selective light responses. By mapping NKCC2 and KCC2 antibody staining on these dendrites, we further show that NKCC2 and KCC2 are preferentially located in the proximal and distal dendritic compartments, respectively. Finally, measurements of the GABA reversal potential in different starburst dendritic compartments indicate that the GABA reversal potential at the distal dendrite is more hyperpolarized than at the proximal dendrite due to KCC2 activity. These results thus demonstrate that the differential distribution of NKCC2 on the proximal dendrites and KCC2 on the distal dendrites of starburst cells results in a GABA-evoked depolarization and hyperpolarization at the NKCC2 and KCC2 compartments, respectively, and underlies the directionally selective light responses of the dendrites. The functional compartmentalization of interneuron dendrites may be an important means by which the nervous system encodes complex information at the subcellular level.direction-selective ͉ GABAergic excitation ͉ interneuron

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Dendritic compartmentalization of chloride cotransporters underlies directional responses of starburst amacrine cells in retina

Gavrikov

Nilson

Dmitriev

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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119

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“…These include geometrical properties of starburst dendrites that lead to biophysical properties that favor centripetal movement (Borg-Graham and Grzywacz 1992;Tukker et al 2004); asymmetric distribution of chloride co-transporters along the dendrites that lead to spatially asymmetric chloride currents and hence to directional asymmetries (Gavrikov et al 2003); or cell-internal biochemical processes, calcium-induced calcium currents, which lead to stronger calcium signals for outward movement (Barlow 1996). These mechanisms are consistent with each other and could function synergistically.…”

Section: Introductionmentioning

confidence: 86%

Symmetric Interactions Within a Homogeneous Starburst Cell Network Can Lead to Robust Asymmetries in Dendrites of Starburst Amacrine Cells

Münch

Werblin²

2006

Journal of Neurophysiology

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Mü nch, Thomas A. and Frank S. Werblin. Symmetric interactions within a homogeneous starburst cell network can lead to robust asymmetries in dendrites of starburst amacrine cells. J Neurophysiol 96: 471-477, 2006. First published April 5, 2006 doi:10.1152/jn.00628.2005. Starburst amacrine cells in the mammalian retina respond asymmetrically to movement along their dendrites; centrifugal movement elicits stronger responses in each dendrite than centripetal movement. It has been suggested that the asymmetrical response can be attributed to intrinsic properties of the processes themselves. But starburst cells are known to release and have receptors for both GABA and acetylcholine. We tested whether interactions within the starburst cell network can contribute to their directional response properties. In a computational model of interacting starburst amacrine cells, we simulated the response of individual dendrites to moving light stimuli. By setting the model parameters for "synaptic connection strength" (cs) to positive or negative values, overlapping starburst dendrites could either excite or inhibit each other. For some values of cs, we observed a very robust inward/outward asymmetry of the starburst dendrites consistent with the reported physiological findings. This is the case, for example, if a starburst cell receives inhibition from other starburst cells located in its surround. For other values of cs, individual dendrites can respond best either to inward movement or respond symmetrically. A properly wired network of starburst cells can therefore account for the experimentally observed asymmetry of their response to movement, independent of any internal biophysical or biochemical properties of starburst cell dendrites. I N T R O D U C T I O NThe starburst amacrine cell, a retinal interneuron, plays a critical role in the circuit of direction-selective (DS) ganglion cells (Fried et al. 2002(Fried et al. , 2005Yoshida et al. 2001). DS cells spike vigorously when a visual stimulus transverses their receptive field in one direction but remain silent when the same stimulus travels in the opposite direction (Barlow and Levick 1965). Individual dendrites of starburst cells also show directional responses (Euler et al. 2002): The observed calcium signal in the tip of starburst dendrites was strongest when motion was directed "outward, " or centrifugal, i.e., from the cell body to the tip of the process. The response was minimal for opposite movement (inward, centripetal, from the tip to the cell body). This makes starburst cell dendrites some of the earliest components in the DS circuit that express directional response properties.Several possible explanations of this phenomenon have been given. These include geometrical properties of starburst dendrites that lead to biophysical properties that favor centripetal movement (Borg-Graham and Grzywacz 1992;Tukker et al. 2004); asymmetric distribution of chloride co-transporters along the dendrites that lead to spatially asymmetric chloride currents and hence to directi...

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“…This role is more akin to that of somatic Kv3 channels in facilitating faithful high-frequency repetitive firing and different from that suggested below for Kv3 channels in starburst cells. Although it is still controversial whether starburst amacrine cells in the adult retina have the ability to produce action potentials (Bloomfield, 1992;Taylor and Wässle, 1995;Peters and Masland, 1996;Zhou and Fain, 1996;Cohen, 2001;Gavrikov et al, 2003), they are clearly not repetitive firing neurons, indicating that Kv3 channels play a novel role in these cells.…”

Section: Expression Of Kv3 Proteins In Starburst Cell Dendritesmentioning

confidence: 99%

A Unique Role for Kv3 Voltage-Gated Potassium Channels in Starburst Amacrine Cell Signaling in Mouse Retina

Ozaita¹,

Petit-Jacques²,

Völgyi³

et al. 2004

J. Neurosci.

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Direction-selective retinal ganglion cells show an increased activity evoked by light stimuli moving in the preferred direction. This selectivity is governed by direction-selective inhibition from starburst amacrine cells occurring during stimulus movement in the opposite or null direction. To understand the intrinsic membrane properties of starburst cells responsible for direction-selective GABA release, we performed whole-cell recordings from starburst cells in mouse retina. Voltage-clamp recordings revealed prominent voltagedependent K ϩ currents. The currents were mostly blocked by 1 mM TEA, activated rapidly at voltages more positive than Ϫ20 mV, and deactivated quickly, properties reminiscent of the currents carried by the Kv3 subfamily of K ϩ channels. Immunoblots confirmed the presence of Kv3.1 and Kv3.2 proteins in retina and immunohistochemistry revealed their expression in starburst cell somata and dendrites. The Kv3-like current in starburst cells was absent in Kv3.1-Kv3.2 knock-out mice. Current-clamp recordings showed that the fast activation of the Kv3 channels provides a voltage-dependent shunt that limits depolarization of the soma to potentials more positive than Ϫ20 mV. This provides a mechanism likely to contribute to the electrical isolation of individual starburst cell dendrites, a property thought essential for direction selectivity. This function of Kv3 channels differs from that in other neurons where they facilitate highfrequency repetitive firing. Moreover, we found a gradient in the intensity of Kv3.1b immunolabeling favoring proximal regions of starburst cells. We hypothesize that this Kv3 channel gradient contributes to the preference for centrifugal signal flow in dendrites underlying direction-selective GABA release from starburst amacrine cells

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Cation–chloride cotransporters mediate neural computation in the retina

Cited by 72 publications

References 36 publications

Dendritic compartmentalization of chloride cotransporters underlies directional responses of starburst amacrine cells in retina

Dendritic compartmentalization of chloride cotransporters underlies directional responses of starburst amacrine cells in retina

Symmetric Interactions Within a Homogeneous Starburst Cell Network Can Lead to Robust Asymmetries in Dendrites of Starburst Amacrine Cells

A Unique Role for Kv3 Voltage-Gated Potassium Channels in Starburst Amacrine Cell Signaling in Mouse Retina

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