Etomidate reduces initiation of backpropagating dendritic action potentials: implications for sensory processing and synaptic plasticity during anesthesia
| Autor: | Joao Bacelo, Leonel Gómez, Jacob Engelmann, Erwin H. van den Burg, Kirsty Grant |
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| Rok vydání: | 2007 |
| Předmět: |
Physiology
Action Potentials Membrane Potentials/drug effects Neural backpropagation Action Potentials/drug effects Membrane Potentials GABA Antagonists Postsynaptic potential Hypnotics and Sedatives Anesthesia Drug Interactions Etomidate Electric Stimulation/methods Electric Fish/anatomy & histology Action potential initiation Neurons Electric Organ Radiation Electric Organ/cytology Neuronal Plasticity Chemistry General Neuroscience Afferent Pathways/drug effects Neuronal Plasticity/drug effects Etomidate/pharmacology medicine.anatomical_structure GABA Antagonists/pharmacology Membrane Potentials/physiology Shunting inhibition Bicuculline/pharmacology Afferent/cytology Afferent Pathways/physiology Parallel fiber In Vitro Techniques Inhibitory postsynaptic potential Bicuculline Hypnotics and Sedatives/pharmacology Dose-Response Relationship Membrane Potentials/radiation effects Dendrites/drug effects Afferent Pathways/cytology medicine Animals Neurons Afferent Afferent Pathways Dose-Response Relationship Radiation Dendrites GABA receptor antagonist Neuronal Plasticity/physiology Electric Stimulation Excitatory Amino Acid Antagonists/pharmacology Afferent/drug effects Inhibitory Postsynaptic Potentials Synaptic plasticity Electric Fish/physiology Neuroscience Excitatory Amino Acid Antagonists Electric Fish |
| Zdroj: | Journal of neurophysiology. 97(3) |
| ISSN: | 0022-3077 |
| Popis: | Anesthetics may induce specific changes that alter the balance of activity within neural networks. Here we describe the effects of the GABAAreceptor potentiating anesthetic etomidate on sensory processing, studied in a cerebellum-like structure, the electrosensory lateral line lobe (ELL) of mormyrid fish, in vitro. Previous studies have shown that the ELL integrates sensory input and removes predictable features by comparing reafferent sensory signals with a descending electromotor command-driven corollary signal that arrives in part through parallel fiber synapses with the apical dendrites of GABAergic interneurons. These synapses show spike timing–dependent depression when presynaptic activation is associated with postsynaptic backpropagating dendritic action potentials. Under etomidate, almost all neurons become tonically hyperpolarized. The threshold for action potential initiation increased for both synaptic activation and direct intracellular depolarization. Synaptically evoked inhibitory postsynaptic potentials (IPSPs) were also strongly potentiated and prolonged. Current source density analysis showed that backpropagation of action potentials through the apical dendritic arborization in the molecular layer was reduced but could be restored by increasing stimulus strength. These effects of etomidate were blocked by bicuculline or picrotoxin. It is concluded that etomidate affects both tonic and phasic inhibitory conductances at GABAAreceptors and that increased shunting inhibition at the level of the proximal dendrites also contributes to increasing the threshold for action potential backpropagation. When stimulus strength is sufficient to evoke backpropagation, repetitive association of synaptic excitation with postsynaptic action potential initiation still results in synaptic depression, showing that etomidate does not interfere with the molecular mechanism underlying plastic modulation. |
| Databáze: | OpenAIRE |
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