Mild hypoxia affects synaptic connectivity in cultured neuronal networks

• Published in: Brain research 2014-04, Vol.1557, p.180-189
• Main Authors: Hofmeijer, Jeannette, Mulder, Alex T.B, Farinha, Ana C, van Putten, Michel J.A.M, le Feber, Joost
• Format: Article
• Language: English
• Subjects: Action Potentials - physiology; Animals; Animals, Newborn; Biological and medical sciences; Cell Culture Techniques - instrumentation; Cells, Cultured; Chronic mild ischemia; Cognitive impairment; Cultured neuronal networks; Electric Stimulation; Female; Functional connectivity; Fundamental and applied biological sciences. Psychology; Hypoxia - physiopathology; Male; Microelectrodes; Neurology; Neurons - physiology; Rats; Synapses - physiology; Synaptic connectivity; Synaptic failure; Time Factors; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2014.02.027

Abstract Eighty percent of patients with chronic mild cerebral ischemia/hypoxia resulting from chronic heart failure or pulmonary disease have cognitive impairment. Overt structural neuronal damage is lacking and the precise cause of neuronal damage is unclear. As almost half of the cerebral energy consumption is used for synaptic transmission, and synaptic failure is the first abrupt consequence of acute complete anoxia, synaptic dysfunction is a candidate mechanism for the cognitive deterioration in chronic mild ischemia/hypoxia. Because measurement of synaptic functioning in patients is problematic, we use cultured networks of cortical neurons from new born rats, grown over a multi-electrode array, as a model system. These were exposed to partial hypoxia (partial oxygen pressure of 150 Torr lowered to 40–50 Torr) during 3 ( n =14) or 6 ( n =8) hours. Synaptic functioning was assessed before, during, and after hypoxia by assessment of spontaneous network activity, functional connectivity, and synaptically driven network responses to electrical stimulation. Action potential heights and shapes and non-synaptic stimulus responses were used as measures of individual neuronal integrity. During hypoxia of 3 and 6 h, there was a statistically significant decrease of spontaneous network activity, functional connectivity, and synaptically driven network responses, whereas direct responses and action potentials remained unchanged. These changes were largely reversible. Our results indicate that in cultured neuronal networks, partial hypoxia during 3 or 6 h causes isolated disturbances of synaptic connectivity.