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Dual Electrophysiological Recordings of Synaptically-evoked Astroglial and Neuronal Responses in Acute Hippocampal Slices
Published on: November 26, 2012
Suppression of presynaptic calcium currents by hypoxia in hippocampal tissue slices
1Division of Neurosurgery, Duke University Medical Center, Durham, NC 27710.
Abstract:
We tested the hypothesis that suppression of inward calcium current in presynaptic terminals is the cause of failure of synaptic transmission early during cerebral hypoxia. Postsynaptic responses in CA1 zone of hippocampal tissue slices were blocked either by the combined administration of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 3-((+-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP) or by lowering extracellular calcium concentration ([Ca2+]o). Repetitive orthodromic activation of central neurons caused transient decrease of [Ca2+]o (measured by ion selective microelectrodes) in neuropil, attributable to influx of Ca2+ in presynaptic terminals. Presynaptic [Ca2+]o responses were rapidly and reversibly suppressed when oxygen was withdrawn from hippocampal tissue slices. The 'resting' baseline level of [Ca2+]o declined at first gradually, then precipitously as in spreading depression (SD). Presynaptic volleys during high frequency train stimulation were also depressed somewhat before SD began. We conclude that (1) presynaptic Ca2+ currents fail during hypoxia, perhaps because 'resting' intracellular free Ca2+ activity is increased and, in part, also because of partial failure of presynaptic impulse conduction; (2) the influx of Ca2+ into brain cells in hypoxic spreading depression is not mediated by glutamate/aspartate dependent channels.
Insights
Hypoxia impairs presynaptic calcium currents, causing synaptic transmission failure. This occurs before spreading depression and is not mediated by glutamate receptors.
Area of Science:
- Neuroscience
- Neurophysiology
- Cellular Neuroscience
Background:
- Synaptic transmission is crucial for brain function.
- Cerebral hypoxia can lead to synaptic failure.
- The role of presynaptic calcium currents in hypoxia-induced synaptic failure requires clarification.
Purpose of the Study:
- To investigate if suppressed inward calcium current in presynaptic terminals causes synaptic transmission failure during early cerebral hypoxia.
- To determine the mechanisms underlying calcium influx during hypoxic spreading depression.
Main Methods:
- Hippocampal tissue slices were used to study synaptic responses.
- Extracellular calcium concentration ([Ca2+]o) was measured using ion-selective microelectrodes.
- Synaptic transmission was blocked using specific antagonists (DNQX and CPP) or by altering extracellular calcium.
Main Results:
- Presynaptic calcium responses were rapidly and reversibly suppressed upon oxygen withdrawal.
- A transient decrease in [Ca2+]o was observed in the neuropil during neuronal activation, indicating Ca2+ influx into presynaptic terminals.
- The 'resting' extracellular calcium level declined, preceding spreading depression.
- Presynaptic volleys were depressed before the onset of spreading depression.
Conclusions:
- Presynaptic calcium currents fail during hypoxia, potentially due to increased intracellular free Ca2+ and impaired impulse conduction.
- Calcium influx into brain cells during hypoxic spreading depression is not mediated by glutamate/aspartate dependent channels.
