Sense and Insensibility – An Appraisal of the Effects of Clinical Anesthetics on Gastropod and Cephalopod Molluscs as a Step to Improved Welfare of Cephalopods

Recent progress in animal welfare legislation stresses the need to treat cephalopod molluscs, such as Octopus vulgaris, humanely, to have regard for their wellbeing and to reduce their pain and suffering resulting from experimental procedures. Thus, appropriate measures for their sedation and analgesia are being introduced. Clinical anesthetics are renowned for their ability to produce unconsciousness in vertebrate species, but their exact mechanisms of action still elude investigators. In vertebrates it can prove difficult to specify the differences of response of particular neuron types given the multiplicity of neurons in the CNS. However, gastropod molluscs such as Aplysia, Lymnaea, or Helix, with their large uniquely identifiable nerve cells, make studies on the cellular, subcellular, network and behavioral actions of anesthetics much more feasible, particularly as identified cells may also be studied in culture, isolated from the rest of the nervous system. To date, the sorts of study outlined above have never been performed on cephalopods in the same way as on gastropods. However, criteria previously applied to gastropods and vertebrates have proved successful in developing a method for humanely anesthetizing Octopus with clinical doses of isoflurane, i.e., changes in respiratory rate, color pattern and withdrawal responses. However, in the long term, further refinements will be needed, including recordings from the CNS of intact animals in the presence of a variety of different anesthetic agents and their adjuvants. Clues as to their likely responsiveness to other appropriate anesthetic agents and muscle relaxants can be gained from background studies on gastropods such as Lymnaea, given their evolutionary history

State Transitions Within The Cortex Are Strongly Influenced By Local Interactions Under General Anesthesia

General anesthetics are a class of drugs with diverse molecular mechanisms that cause a state of unconsciousness. Generally, anesthetics are thought to exert this effect by co- opting endogenous sleep pathways within the brain, and activity patterns recorded during anesthesia resemble those recorded during natural sleep. Monitors of anesthetic depth take advantage of the relationship between brain activity patterns and anesthetic concentration to define a depth of exposure. Recovery from anesthetic-induced unconsciousness is typically assumed to be a passive, linear process that relies upon elimination of drug from the body. However, it has been shown that activity patterns undergo discrete transitions between several distinct brain states under anesthesia. Furthermore, the brain exhibits a resistance to recovery of consciousness during emergence from anesthesia. Together, these results show that emergence cannot be explained by drug elimination alone. In this dissertation, we present evidence to suggest that stochastic fluctuations between distinct brain states account for this resistance to emergence. Furthermore, we show evidence to suggest that local cortical interactions are the principal organizing mechanism that gives rise to the brain states and state transitions recorded under general anesthesia. This mechanism is distinct from those known to drive state transitions during natural sleep. During sleep, broadly projecting modulatory pathways engage neurons throughout the thalamocortical network in coherent activity patterns and state transitions. Here, we demonstrate local heterogeneity in activity patterns and transition times within the cortex. Furthermore, our results indicate that, despite there being only weak coupling between activity patterns and transition times between different cortical regions, this coupling is sufficient to give rise to global brain states. Altogether, the work presented in this dissertation indicates that the nature of oscillations within the cortex is strongly influenced by local interactions. This finding suggests that the mechanisms thought to give rise to state transitions during sleep are not the same as those that give rise to transitions under anesthesia. This finding that local interactions are potentially a stronger organizing mechanism for cortical activity than previously appreciated has important implications for anesthetic monitoring, clinical sleep disorders, and our basic understanding of thalamocortical activity patterns

Advances in Clinical Neurophysiology

Including some of the newest advances in the field of neurophysiology, this book can be considered as one of the treasures that interested scientists would like to collect. It discusses many disciplines of clinical neurophysiology that are, currently, crucial in the practice as they explain methods and findings of techniques that help to improve diagnosis and to ensure better treatment. While trying to rely on evidence-based facts, this book presents some new ideas to be applied and tested in the clinical practice. Advances in Clinical Neurophysiology is important not only for the neurophysiologists but also for clinicians interested or working in wide range of specialties such as neurology, neurosurgery, intensive care units, pediatrics and so on. Generally, this book is written and designed to all those involved in, interpreting or requesting neurophysiologic tests

Deep Brain Stimulation (DBS) Applications

The issue is dedicated to applications of Deep Brain Stimulation and, in this issue, we would like to highlight the new developments that are taking place in the field. These include the application of new technology to existing indications, as well as ‘new’ indications. We would also like to highlight the most recent clinical evidence from international multicentre trials. The issue will include articles relating to movement disorders, pain, psychiatric indications, as well as emerging indications that are not yet accompanied by clinical evidence. We look forward to your expert contribution to this exciting issue

Propofol and Sevoflurane Differentially Modulate Cortical Depolarization following Electric Stimulation of the Ventrobasal Thalamus

The neuronal mechanisms how anesthetics lead to loss of consciousness are unclear. Thalamocortical interactions are crucially involved in conscious perception; hence the thalamocortical network might be a promising target for anesthetic modulation of neuronal information pertaining to arousal and waking behavior. General anesthetics affect the neurophysiology of the thalamus and the cortex but the exact mechanisms of how anesthetics interfere with processing thalamocortical information remain to be elucidated. Here we investigated the effect of the anesthetic agents sevoflurane and propofol on thalamocortical network activity in vitro. We used voltage-sensitive dye imaging techniques to analyze the cortical depolarization in response to stimulation of the thalamic ventrobasal nucleus in brain slices from mice. Exposure to sevoflurane globally decreased cortical depolarization in a dose-dependent manner. Sevoflurane reduced the intensity and extent of cortical depolarization and delayed thalamocortical signal propagation. In contrast, propofol neither affected area nor amplitude of cortical depolarization. However, propofol exposure resulted in regional changes in spatial distribution of maximum fluorescence intensity in deep regions of the cortex. In summary, our experiments revealed substance-specific effects on the thalamocortical network. Functional changes of the neuronal network are known to be pivotally involved in the anesthetic-induced loss of consciousness. Our findings provide further evidence that the mechanisms of anesthetic-mediated loss of consciousness are drug- and pathway-specific