ABSTRACT
BACKGROUND: Anesthetics have a profound influence on a myriad of autonomic processes. Mechanisms of general anesthesia, and how these mechanisms give rise to the multifaceted state of anesthesia, are largely unknown. The ascending and descending serotonin (5-HT) networks are key modulators of autonomic pathways, and are critically involved in homeostatic reflexes across the motor, somatosensory, limbic and autonomic systems. These 5-HT networks are thought to contribute to anesthetic effects, but how anesthetics affect 5-HT neuron function remains a pertinent question. We hypothesized that the volatile anesthetic isoflurane inhibits action potential discharge of medullary raphé 5-HT neurons. METHODS: We conducted extracellular recordings on individual neurons in the medullary raphé region of the unanesthetized in situ perfused brainstem preparation to determine how exposure to isoflurane affects 5-HT neurons. We examined changes in 5-HT neuron baseline firing in response to treatment with either 1, 1.5, or 2% isoflurane. We measured isoflurane concentrations by gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Exposure to isoflurane inhibited action potential discharge in raphé 5-HT neurons. We document a concentration-dependent inhibition over a range of concentrations approximating isoflurane MAC (minimum alveolar concentration required for surgical anesthesia). Delivered concentrations of isoflurane were confirmed using GC-MS analysis. CONCLUSIONS: These findings illustrate that halogenated anesthetics greatly affect 5-HT neuron firing and suggest 5-HT neuron contributions to mechanisms of general anesthesia.
Subject(s)
Anesthetics, Inhalation/pharmacology , Isoflurane/pharmacology , Neural Inhibition/drug effects , Raphe Nuclei/drug effects , Serotonergic Neurons/drug effects , Action Potentials/drug effects , Animals , Dose-Response Relationship, Drug , Gas Chromatography-Mass Spectrometry , Homeostasis/drug effects , Homeostasis/physiology , Male , Microelectrodes , Neural Inhibition/physiology , Raphe Nuclei/physiology , Rats, Sprague-Dawley , Serotonergic Neurons/physiology , Tissue Culture TechniquesABSTRACT
Neurones that lose their presynaptic partners because of injury usually retract or die. However, when the auditory interneurones of the cricket Gryllus bimaculatus are denervated, dendrites respond by growing across the midline and forming novel synapses with the opposite auditory afferents. Suppression subtractive hybridization was used to detect transcriptional changes 3 days after denervation. This is a stage at which we demonstrate robust compensatory dendritic sprouting. Whereas 49 unique candidates were down-regulated, no sufficiently up-regulated candidates were identified at this time point. Several candidates identified in this study are known to influence the translation and degradation of proteins in other systems. The potential role of these factors in the compensatory sprouting of cricket auditory interneurones in response to denervation is discussed.
