Abstract
Subcellular difference in the reversal potential of Cl− (ECl) has been found in many types of neurons. As local ECl largely determines the action of nearby GABAergic/glycinergic synapses, subcellular ECl difference can effectively regulate neuronal computation. The ON-OFF retinal ganglion cell (RGC) processes both ON and OFF visual signals via its ON and OFF dendrites, respectively. It is thus interesting to investigate whether the ON and OFF dendrites of single RGCs exhibit different local ECl. Here, using in vivo gramicidin-perforated patch recording in larval zebrafish ON-OFF RGCs, we examine local ECl at the ON and OFF dendrites, and soma through measuring light-evoked ON and OFF inhibitory responses, and GABA-induced response at the soma, respectively. We find there are subcellular ECl differences between the soma and dendrite, as well as between the ON and OFF dendrites of single RGCs. These somato-dendritic and inter-dendritic ECl differences are dependent on the Cl− extruder, K+/Cl− co-transporter (KCC2), because they are largely diminished by down-regulating kcc2 expression with morpholino oligonucleotides (MOs) or by blocking KCC2 function with furosemide. Thus, our findings indicate that there exists KCC2-dependent ECl difference between the ON and OFF dendrites of individual ON-OFF RGCs that may differentially affect visual processing in the ON and OFF pathways.
Highlights
Intracellular Cl− homeostasis is involved in the regulation of many cellular functions, including cell volume and membrane excitability (Blaesse et al, 2009)
Similar to other species (Gao and Wu, 1998; Pang et al, 2003), light-evoked responses (LERs) of zebrafish ON-OFF retinal ganglion cell (RGC) could be temporally divided into two synaptic components after the onset of the responses (Figure 1)
The late component (150–200 ms after the LER onset) was reversed around −60 mV, similar to the theoretical examined Cl− reversal potential (ECl) according to the Nernst equation (Figure 1B), supporting the notion that this component was mediated by GABAergic/glycinergic inputs from amacrine cells
Summary
Intracellular Cl− homeostasis is involved in the regulation of many cellular functions, including cell volume and membrane excitability (Blaesse et al, 2009). Differential subcellular distribution of KCC2 and/or NKCC can generate an uneven [Cl−]i gradient along neuronal processes, leading to different GABA actions on the same neuron (Vardi et al, 2000; Khirug et al, 2005; Duebel et al, 2006; Gavrikov et al, 2006). The dendrite and axon of ON bipolar cells preferentially express NKCC and KCC2, respectively (Vardi et al, 2000; Duebel et al, 2006), resulting in a depolarization action of synaptic inputs from horizontal cells to BC dendrites and a hyperpolarization action of synaptic inputs from amacrine cells to BC axons. Non-uniform subcellular distribution of KCC2 and/or NKCC in retinal cells can regulate visual information processing
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