Determining the spatial and temporal dynamics of sensory and motor networks in the intact system is necessary for a complete understanding of the functional architecture of the mammalian brain. Imaging of voltage-sensitive dye signals applied in vivo offer excellent spatial and temporal resolution of spontaneous and evoked responses and permits one to monitor the activity of large networks during cortical processing. Using the rat barrel cortex as a model system I will present a method for imaging the subthreshold activity of a population of neurons located in layers 2/3 and show the spatiotemporal characteristics of whisker-evoked responses. Combining voltage-sensitive dye imaging with simultaneous whole-cell patch clamp recording allows investigation of the correlation between the measured voltage-sensitive dye signals and membrane potential activity, particularly specific correlations with sub- and suprathreshold activity. These recordings have provided insights into the exact nature of the voltage-sensitive dye imaging signals. Further insights into the function of cortical networks will come with combination of recordings of the activity of networks of neurons with selective manipulation of cellular activity by in vivo infection of populations of neurons with viral constructs. To this end we have used both intrinsic optical signals and mapping of extracellular electrical activity to deliver lenti viral vectors into defined cortical columns representing specific individual whiskers. These targeted lenti viral injections allow identification of the anatomy of large numbers of cells involved in the generation of the recorded voltage-sensitive dye signals. Furthermore it allows the potential for specific manipulation of cellular properties with the objective of influencing selective populations of cortical neurons at specific stations in the sensory processing pathway in the cortex.