Shift of chloride reversal potential in neurons of the accessory optic system in albinotic rats

Albinism affects the anatomy and physiology of the visual system in mammals. Behavioural, anatomical and in vivo electrophysiological investigations revealed that the optokinetic reflex is abnormal and retinal slip neurons in the nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic system (NOT-DTN) lack direction selectivity and have a reduced dendritic tree in albinotic rats and ferrets. Earlier investigations show a disturbed chloride homeostasis and a depolarizing action of GABAergic currents in visual cortex cells of albinotic rats. We assume that an altered local inhibition could be one critical factor explaining the loss of direction selectivity in DTN neurons. To test this patch clamp analysis of NO-TDTN neurons in 250 μm thick acute brain slices from pigmented and albinotic rats were performed. GABAergic IPSCs were elicited by lateral current stimulation and the reversal potentials of GABA(A-) mediated currents (E(GABA)) were determined. Our results show a significantly more negative E(GABA) in NOT-DTN neurons of pigmented (-62.1 mV, ±10.8 mV, n=24) than of albinotic rats (-49.2 mV, ±17.7 mV, n=19; P<0.001). Control measurements in the superficial layer of the superior colliculus revealed no significant differences between pigmented (-56.2 mV, ±16.4 mV, n=17) and albinotic rats (-60.7 mV, ±13.8 mV, n=28; P>0.324). A similar shift in reversal potential of GABA(A-)mediated currents was observed also in pyramidal cells in layers II/III and V of the visual cortex and was explained by an accumulation of intracellular chloride due to an abnormal activity of chloride co-transporters. As described for retinal ganglion cells and cortical neurons, direction selectivity is formed by a balanced excitatory and inhibitory input. Our combined data suggest that the observed shift in reversal potential and a possible dysfunction of inhibitory interneurons might indeed be one factor responsible for the reduction of direction selectivity in the NOT-DTN and therefore for the pathology of the optokinetic response in albino mammals.