The input layer of the basal ganglia, the striatum, plays a critical role in the control of motor behaviour and cognitive function. It serves as a filter for cortical and thalamic signals and takes part in determining which actions should be performed at a given instant. Our goal is to define the cellular and network organisation underlying decision-making by analysing the microcircuitry of subpopulations of neurons in striatum (interneurons and projection neurons) concerned with the control of different patterns of behaviour, and their input from cortex (pallium), thalamus and the modulatory inputs from dopaminergic, histaminergic and 5-HT neurons. The microcircuitry will be studied in slices of striatum with patch electrode recordings from three or more identified subtypes of neurons at the same time, while synaptic and membrane properties are investigated and also the synaptic response to the different input systems. Specific synaptic connections of the recorded neurons will be identified by electron microscopy and quantitative aspects of the connections of the different classes of neurons will be defined. Striatal neuronal activity will also be studied in behaving animals with multiunit neuronal recording in relation to defined motor behaviours utilizing several vertebrate model systems (lamprey, rodent and primate). The primary focus will be on striato-pallidal projections indirectly controlling motor programs at the brainstem/spinal cord level, rather than via the thalamo-cortical forebrain projections since these projections cannot as easily be interpreted. Neuronal function and synaptic interaction at the microcircuit level will be subjected to a detailed computer modelling based directly on the outcome of the experimental analyses. Plasticity underlying motor learning/synaptic plasticity, particularly in relation to the dopaminergic, 5-HT and histaminergic inputs will also be characterized.