Synaptic feedback excitation has hypothalamic neural networks generate quasirhythmic burst activity.
1. Dissociated neurons from embryonic rat hypothalamus form synaptically coupled networks when cultured for several weeks. When synaptic inhibition is suppressed by the gamma-aminobutyric acid-A (GABAA) antagonist picrotoxin, neurons exhibit "rhythmic" burst activity that is blocked by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 2. We have examined whether this type of activity is generated by pacemaker cells driving follower cells synaptically or whether it is generated by a neuronal network through feedback excitation by Ca2+ imaging of Fura-2/AM-loaded neurons and single-cell recording. 3. IN the presence of the GABAA antagonist picrotoxin (20 microM), a large majority of neurons (> 85%) displayed quasirhythmic increases in intracellular concentration of Ca2+ ([Ca2+]i). Single-cell recording revealed that these increases in [Ca2+]i correspond to burst discharges in individual neurons. When excitatory synaptic transmission was blocked by CNQX (20 microM), none of the imaged neurons exhibited significant oscillations in [Ca2+]i. 4. Investigation of the intervals between bursts from single-cell recording revealed a random distribution over a range of 400% from the minimum interval. Poincaré maps of burst intervals, i.e., graphs of all burst intervals versus their preceding burst interval, revealed that a burst interval is unpredictable from its predecessor. 5. When synaptic coupling was attenuated by low concentrations of CNQX (50-500 nM), the mean burst interval was considerably increased without a change in the random character of burst activity. 4-Aminopyridine (1 mM), known to increase synaptic efficiency, reduced the mean burst interval.(ABSTRACT TRUNCATED AT 250 WORDS)
Müller
W
W
Max-Planck-Institut für Biophysikalische Chemie, Abt. Membranbiophysik, AG Zellphysiologie, Göttingen, Germany.
Swandulla
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D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004594:Electrophysiology; D005246:Feedback; D007031:Hypothalamus / Q000502:physiology*; D007425:Intracellular Membranes / Q000378:metabolism; D009415:Nerve Net / Q000502:physiology*; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002118:Calcium