Even though anesthetics are widely used in the medical practice, there are still unresolved issues which relate to their mechanisms of action and therefore to their ability to induce loss of consciousness. Since a large number of very different chemical molecules are used in general anesthesia, a large variety of potential molecular targets might exist. Some of these might relate to axonal conduction and membrane excitability. In some cases, this action could either occur at the presynaptic level, modifying the neurotransmitter release and reuptake machineries, or at the postsynaptic level, modifying the number and/or sensitivity of post-synaptic receptors. These functional alterations might also selectively affect one or more specific neuronal phenotypes. Nevertheless, despite the complexity of their molecular targets, all general anesthetics induce a profound inhibition of the awake functions without suppressing the cortical EEG activity and sparing evoked cortical responses. Therefore, anesthetics should lead to the loss of consciousness by altering the signal processing of the brain, rather than by abolishing its activity. Based on these considerations, I began the investigation of the electrophysiological alterations induced by various classes of general anesthetics, on the activity of the rat visual system to uncover some aspects of their mechanisms of action. In this project I compared the effects of three states of anesthesia induced by two different molecules, sevofluorane, a volatile general anesthetic, and propofol, which is intravenously injected. For these experiments rats were curarized, mechanically ventilated and the body temperature was controlled. During states of anesthesia, visual evoked potentials were recorded by means of superficial electrodes implanted in the skull. Two functional properties of the visual processing were evaluated: i) the sensitivity to stimuli of different brightness and ii) the dichotomy of the ON/OFF response, which is essential for contrast detection. Moreover, the EEG resting activity was recorded. The preliminary results showed that the overall basal cortical activity was reduced in a comparative manner between the two drugs throughout the three states of anesthesia. Otherwise, significant differences were found in the power of alpha and gamma EEG oscillations and in the effects on the visual evoked activity, suggesting the presence of two very distinct circuital mechanisms of action and providing novel information about the ability of anesthetics to induce loss of consciousness.

EFFECTS OF GENERAL ANESTHETICS ON VISUAL CORTEX EVOKED AND RESTING ACTIVITY / A. Arena ; tutor: A. Malgaroli ; coordinatore: M. Mazzanti. UNIVERSITA' DEGLI STUDI DI MILANO, 2014 Jun 12. 26. ciclo, Anno Accademico 2013. [10.13130/arena-alessandro_phd2014-06-12].

EFFECTS OF GENERAL ANESTHETICS ON VISUAL CORTEX EVOKED AND RESTING ACTIVITY

A. Arena
2014

Abstract

Even though anesthetics are widely used in the medical practice, there are still unresolved issues which relate to their mechanisms of action and therefore to their ability to induce loss of consciousness. Since a large number of very different chemical molecules are used in general anesthesia, a large variety of potential molecular targets might exist. Some of these might relate to axonal conduction and membrane excitability. In some cases, this action could either occur at the presynaptic level, modifying the neurotransmitter release and reuptake machineries, or at the postsynaptic level, modifying the number and/or sensitivity of post-synaptic receptors. These functional alterations might also selectively affect one or more specific neuronal phenotypes. Nevertheless, despite the complexity of their molecular targets, all general anesthetics induce a profound inhibition of the awake functions without suppressing the cortical EEG activity and sparing evoked cortical responses. Therefore, anesthetics should lead to the loss of consciousness by altering the signal processing of the brain, rather than by abolishing its activity. Based on these considerations, I began the investigation of the electrophysiological alterations induced by various classes of general anesthetics, on the activity of the rat visual system to uncover some aspects of their mechanisms of action. In this project I compared the effects of three states of anesthesia induced by two different molecules, sevofluorane, a volatile general anesthetic, and propofol, which is intravenously injected. For these experiments rats were curarized, mechanically ventilated and the body temperature was controlled. During states of anesthesia, visual evoked potentials were recorded by means of superficial electrodes implanted in the skull. Two functional properties of the visual processing were evaluated: i) the sensitivity to stimuli of different brightness and ii) the dichotomy of the ON/OFF response, which is essential for contrast detection. Moreover, the EEG resting activity was recorded. The preliminary results showed that the overall basal cortical activity was reduced in a comparative manner between the two drugs throughout the three states of anesthesia. Otherwise, significant differences were found in the power of alpha and gamma EEG oscillations and in the effects on the visual evoked activity, suggesting the presence of two very distinct circuital mechanisms of action and providing novel information about the ability of anesthetics to induce loss of consciousness.
12-giu-2014
Settore BIO/09 - Fisiologia
anesthetic ; sevoflurane ; propofol ; loss of consciousness ; EEG ; evoked potential ; visual system
MALGAROLI, ANTONIO
MAZZANTI, MICHELE
Doctoral Thesis
EFFECTS OF GENERAL ANESTHETICS ON VISUAL CORTEX EVOKED AND RESTING ACTIVITY / A. Arena ; tutor: A. Malgaroli ; coordinatore: M. Mazzanti. UNIVERSITA' DEGLI STUDI DI MILANO, 2014 Jun 12. 26. ciclo, Anno Accademico 2013. [10.13130/arena-alessandro_phd2014-06-12].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/238236
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