Dumanska H. Neurotransmission between retinal ganglion cells and superficial superior colliculus neurons in coculture in normal and hypoxic conditions

Properties of synaptic transmission at cocultivated retinocollicular synapses in normal and hypoxic conditions were studied. Glutamatergic excitatory synaptic transmission in cocultivated retinocollicular synapses is mediated by NMDA and AMPA receptors. GABAergic inhibitory neurotransmission is mediated by GABAA receptors. The release of glutamate and GABA at retinocollicular synapses demonstrated a quantal nature. The release properties of these neurotransmitters can be adequately described by simple binomial statistics. Paired pulse depression of glutamatergic and paired pulse potentiation of GABAergic cocultivated retinocollicular synaptic transmission were predominantly caused by presynaptic mechanisms. We conducted a series of experiments to characterize the effect and define the mechanisms of hypoxia on synaptic transmission in cocultivated retinocollicular synapses. Application of hypoxic solution led to a long lasting potentiation (LTP) of NMDAR-mediated synaptic transmission. Analysis of the oxygen deficiency effect on the spontaneous and miniature postsynaptic currents (sPSC and mPSC respectively) revealed an increase in the frequency of their occurrence and the appearance of the second peak in the mPSC histogram distribution. The assessment of quantum and binomial parameters reflects presynaptic changes during the potentiation, independent of the release probability. Most likely this LTP can be caused by an increase in the total number of release sites. Glutamatergic synaptic transmission mediated by AMPA receptors, responded to application of hypoxic solution by the brief reduction, which is the result of presynaptic dysfunction and associates with decrease in the release probability and number of active zones. GABAergic synaptic transmission mediated by activation GABAA receptors, responded to hypoxia by the long term depression (LTD). Analysis of sPSC and mPSC showed a significant decrease in the frequency of their occurrence and significant decrease in the quantal size over a period of oxygen deficiency. In general, the effect of hypoxia-induced LTD of GABAergic synaptic transmission is based on complex changes of presynaptic (independent on the release probability) and postsynaptic (decrease in sensitivity of receptors in the postsynaptic membrane) mechanisms.