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

Abstract

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

Dissociated Gender-Specific Effects of Recurrent Seizures on GABA Signaling in CA1 Pyramidal Neurons: Role of GABAAReceptors

“…Intracellular differences in chloride concentration and KCC2 expression, both across the axonodendritic processes and around extrasynaptic GABA A receptors, have been described previously (Gulyas et al, 2001;Duebel et al, 2006;Gavrikov et al, 2006).…”

Coordinate control of terminal dendrite patterning and dynamics by the membrane protein Raw

“…Finally, dendrite arbors often contain functionally distinct domains as well. For example, the proximal-distal compartmentalization of chloride co-transporters underlies directional selectivity in starburst amacrine cells (Gavrikov et al, 2006). Whereas axon/dendrite compartmentalization can be attributed to neuronal polarization, the developmental origin of dendrite subcompartments is less well understood.…”

Enhanced insulin secretion and improved glucose tolerance in mice with homozygous inactivation of the Na+K+2Cl− co-transporter 1

“…This is partially due to the fact that expression of NKCC2 has been only recently found in extratubular cells. Indeed, NKCC2 is expressed in specialised neurons of the gastrointestinal tract or interneurons (Gavrikov et al 2006, Xue et al 2009, Zhu et al 2011 and in cells of the gastric, intestinal, endolymphatic sac and olfactory epithelia (Akiyama et al 2007, Nickell et al 2007, Nishimura et al 2009, Xue et al 2009, Zhu et al 2011. In fact, low levels of Slc12a1 mRNAs appear to be widely distributed in human tissues (Di Fulvio & Alvarez-Leefmans 2009).…”