ANALYSIS OF THE EFFECTS OF ANESTHETICS ON THE RAT VISUAL CORTEX ACTIVITY

"Even if anesthetics are widely used in the medical practice to ensure the induction and maintenance of general anesthesia, there is still an unresolved issue which relates to their mechanism of action therefore to the nature of their molecular target site(s). Since a large number of very different chemical molecules are used in general anesthesia, this suggests that a large variety of molecular targets must exist. Some of these might affect axonal conduction and membrane excitability. In some cases, this action could either occur at the presynaptic level, modifying the neurotransmitter release and reuptake, or at the postsynaptic level, modifying the receptor sensitivity. These functional alterations might also affect one or more neuronal phenotypes for example by dampening the activity of the Glutamatergic circuits, or by enhancing the activity of GABAergic networks (or other inhibitory systems). Despite the underlying complexity of molecular targets, all general anesthetics induce a general and profound inhibition of cortical EEG activity while sparing evoked cortical responses. Based on these considerations, I decided to begin the investigation of the electrophysiological basis of the action of general anesthetics on the visual thalamus and on cortical circuits for vision in the rat. In this project I will compare the effects of different anesthetic molecules including sevofluorane, propofol and ketamine. Fot these experiments rats are curarized (one bolus of atracurium, 5 mg\/kg, each 20 minutes) and mechanically ventilated by the insertion of a cannula in trachea (the oxygen and CO2 level are continuously monitored). In these experiments I record: i) visual evoked potentials (VEPs) by superficial electrodes implanted in the skull; ii)intracellular visual cortex activity by sharp electrodes; iii) the pattern of activation of neurons in the LGN and cortex by the expression of the c-fos gene protein product known to report neuronal firing; iv) by applying the synaptic biosensor, GreenZip, which has been recently developed in my laboratory, I will record synaptic network activity with single synapse resolution. In these experiments, rats will be visually stimulated with light pulses (20 msec) or with alternating black and white horizontal stripes at constant overall luminance (2Hz reversal, 0.5 cycle\/degree). In a set of preliminary experiments that I will present at the meeting, I have characterized the effect of sevoflurane, a volatile anesthetic . I found that sevofluorane increases in a dose-dependent manner both the amplitude and the latency of VEPs, while the general cortical electrical activity is reduced. Among the working hypotheses I’m exploring : i)an unbalance between inhibition and excitation in thalamic or cortical circuits by the anesthetic ; ii) an increase in the pool of available vesicles for visually evoked activity because of reduced background activity . At the meeting I will present an account on this work describing the methodological approach and my preliminary results."