Short-term hypoxia induces bidirectional pathological long-term plasticity of neurotransmission in visual retinocollicular pathway.

Using the paired patch-clamp technique, we studied the effects of short-term hypoxia on retinocollicular synaptic transmission in an originally-developed coculture of dissociated retinal cells and superficial superior colliculus (SSC) neurons. Pharmacologically isolated N-methyl-D-aspartate receptor (NMDA)-, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA)- and gamma-aminobutyric acid receptor (GABA)-mediated postsynaptic currents (PSCs) were evoked in SSC neurons by generation action potentials in presynaptic retinal ganglion cells. Spontaneous and miniature PSCs were recorded in SSC neurons in the absence of presynaptic stimulation. Short-term (up to 5 min) hypoxia induced long-term potentiation of NMDA transmission, long-term depression of GABA neurotransmission and temporary suppression of AMPA transmission. Also, we observed hypoxia-induced reduction of voltage-dependent magnesium blockade of evoked NMDA response. Evoked, spontaneous and miniature postsynaptic currents were analyzed in terms of a binomial model. This analysis revealed that hypoxia acts mainly presynaptically on excitatory neurotransmission and both pre‒ and postsynaptically on inhibitory retinocollicular transmission. Thus, we showed for the first time hypoxia-induced bidirectional long-term plasticity of the retinocollicular synaptic transmission. The results obtained reflect the electrophysiological basis of hypoxia-involved pathological lesion of the retinocollicular pathway.