In vitro networks: Cortical mechanisms of anaesthetic action

Abstract

In summary, there are good reasons for assuming that anaesthetic-induced synchronization and depression of neuronal activity in the cerebral cortex involve sub-cortical arousal systems. However, as discussed above, we are also faced with data strongly supporting the possibility that direct actions on cortical neurones come into play. How do we evaluate the importance of different potential pathways of drug action? How do we establish a more precise hypothesis that distinguishes between cortical and sub-cortical mechanisms? What type of experiments can be conducted to elucidate the specific contributions made by different local networks? A major problem arises from the fact that distributed local microcircuits are extensively interconnected in intact brains: if can assume that a particular part of the brain, say the neocortex (termed network B in the following) receives excitatory input from a sub-cortical structure (network A), neuronal activity in B may be reduced either because of direct effects on drug targets located in B, or because of a decrease in excitatory drive provided by A. Thus, it is necessary to study drug effects in isolated local networks, which do not receive synaptic input from different brain areas. If it turns out that network B is equally sensitive to drug treatment, regardless of whether synaptic input provided by A is present or not, B is most probably the substrate of drug action. If B is rendered insensitive by removing synaptic input provided by A, the more important effects take place in network A. At this point, the topics addressed above have been considered in order to establish some type of conceptual framework. Such a framework seems to be helpful for recognizing the benefit of brain slice studies and for integrating the results into a general understanding of how anaesthetics work. The research discussed in the following is centred on work dealing with the question of how general anaesthetics alter activity patterns in hippocampal and neocortical brain slices. The focus is on drug actions occurring at the network level.