Title: Hypoxia-induced bidirectional pathological long-term synaptic plasticity in visual retinocollicular pathway

Hanna Dumanska

National Academy of Science of Ukraine, Ukraine


Dr Dumanska Hanna is a Senior Researcher at the Department of Neuronal Networks Physiology, Bogomoletz Institute of Physiology, National Academy of Science of Ukraine, where she has been since 2005. She has expertise in primary cell culturing, in vitro electrophysiological recordings and in statistical analysis. Dumanska completed her PhD in Biophysics in 2016. Her research interests focus on the role of synaptic transmission and plasticity in physiology and pathophysiology context, specifically on the visual retinocollicular synaptic transmission under normal and hypoxic conditions. Dumanska developed an originally-designed primary cell cocultivation method. This method allows to obtain monosynaptic couples of spatially identified pre- and postsynaptic neurons for further electrophysiological recordings. Such approach has been used in her research. She published six first-author papers, got a utility model of “chamber for cocultivation” and participated in up to 15 national and international conferences.


The visual system is extremely sensitive to hypoxia, due to its energy demands. Lesions of the visual system, as a result of injury, toxicity, neurodegenerative and inflammatory processes, metabolic and cardiovascular disease are often mediated or accompanied by a short- or long-term hypoxia. Retinocollicular projections form the initial level of visual signal transmission from the retina to the subcortical visual center (superficial superior colliculus, SSC). Structural and functional responses to hypoxic injury in retinocollicular projections were demonstrated using functional magnetic resonance imaging. Whereas, hypoxia-induced effects on this synaptic transmission were not previously investigated.

 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. Short-term duration of hypoxia permits investigation of the prepathological state that foregoes irreversible hypoxic injury and cell death. Originally designed coculture of dissociated retinal cells and SSC neurons with easily identified synaptic couples of retinal ganglion cell (RGC) – SSC neuron was used as in vitro model of visual retinocollicular pathway. Pharmacologically isolated NMDA−, AMPA− and GABAA−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. Method of fast local superfusion was used for application (up to 5 min) of hypoxic solutions on synaptically connected neurons.

Short-term hypoxia induced long-term potentiation of NMDA transmission, long-term depression of GABAA 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. Physiological role of GABAergic retinocollicular projections is in regulation of activation and plasticity of excitatory NMDAR-mediated transmission. Hypoxia-induced LTD of GABAergic transmission enhances pathological effect of LTP of NMDAR-mediated transmission in retinocollicular synapses and possibly is an additional hypoxia-induced injury of neurotransmission from the retina to subcortical visual center.

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.