Cortical operations are built up from states associated with distinct behaviour-dependent network activity patterns that subserve information aquisition, encoding, memory consolidation and retrieval. Thus, they can be considered as manifestations of different processing modes. Groups of modulatory, largely monoaminergic neurons located in subcortical nuclei innervating all forebrain areas are indispensable for the generation, stabilization and termination of cortical activity states. In recent years the concept of subcortical modulation has been expanded by the discovery of a fast type of modulatory action driving the rapid readjustment of cortical activity and associated behaviours. Thus, cortical networks are under the influence of a tonic, slow, as well as a phasic, rapid component of subcortical modulation that are acting in parallel. Results from our laboratory revealed that the median raphe (MR) nucleus, one of the main sources of serotonergic innervation of the limbic system , besides the non-synaptic diffuse action, also exerts a fast type of modulation via the selective innervation of cortical GABAergic interneurons. This selective effect on local inhibition may be ideal for the synchronous resetting of the target principal cell circuits, or for the continuous tuning of their activity. These discoveries, together with the methodological advances of recent years, enable us to map the neuronal network mechanisms behind transitions of brain states, as well as associated behaviours, induced by subcortical inputs. We will focus on the MR – limbic connection with the aim to unravel the physiological, pharmacological and anatomical features of MR neuronal assemblies, both the slow- and fast-acting, as well as the serotonergic and glutamatergic components (together with their cortical target circuits) that will have been shown - using optic stimulation of ChR2/eGFP virus-infected MR neurons - to evoke characteristic behaviours, such as anxiety and conditioned fear.
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