Hypercapnia modulates synaptic interaction of cultured brainstem neurons.
CO(2) is an important metabolic product whose concentrations are constantly monitored by CO(2) chemoreceptors. However, the high systemic CO(2) sensitivity may not be achieved by the CO(2) chemoreceptors without neuronal network processes. To show modulation of network properties during hypercapnia, we studied brainstem neurons dissociated from embryonic rats (P17-19) in multielectrode arrays (MEA) after initial period (3 weeks) of culture. Spike trains of 33,622 pairs of units were analyzed using peri-event histograms (PEH). The amplitude of peri-central peaks between two CO(2)-stimulated units increased and the peak latency decreased during hypercapnia. Similar enhancement of synaptic strength was observed in those sharing a common input. These phenomena were not seen in CO(2)-unresponsive neurons. The amplitude of peri-central peaks between two CO(2) inhibited units also increased without changing latency. Over 60% CO(2)-stimulated neurons studied received mono-/oligosynaptic inputs from other CO(2)-stimulated cells, whereas only approximately 10% CO(2)-unresponsive neurons had such synaptic inputs. A small number of brainstem neurons showed electrical couplings. The coupling efficiency of CO(2)-stimulated but not CO(2)-unresponsive units was suppressed by approximately 50% with high PCO(2). Inhibitory synaptic projections were also found, which was barely affected by hypercapnia. Consistent with the strengthening of excitatory synaptic connections, CO(2) sensitivity of post-synaptic neurons was significantly higher than presynaptic neurons. The difference was eliminated with blockade of presynaptic input. Based on these indirect assessments of synaptic interaction, our PEH analysis suggests that hypercapnia appears to modulate excitatory synaptic transmissions, especially those between CO(2)-stimulated neurons.
Yang
Liang
L
Department of Biology, Georgia State University, 33 Gilmer Street, Atlanta, GA 30303, USA.
Su
Junda
J
Zhang
Xiaoli
X
Jiang
Chun
C
D000704:Analysis of Variance; D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism*; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000166:cytology / Q000378:metabolism*; D004594:Electrophysiology; D006935:Hypercapnia / Q000378:metabolism*; D009415:Nerve Net / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D009435:Synaptic Transmission / Q000502:physiology*
D002245:Carbon Dioxide