Voltage-sensitive dye imaging of neocortical spatiotemporal dynamics to afferent activation frequency

The spatial and temporal patterns of neocortex activation are determined no t only by the dynamic character of the input but also by the intrinsic dyna mics of the cortical circuitry. To study the role of afferent input frequen cy on cortical activation dynamics, the electrical activity of in vitro neo cortex slices was imaged during white-matter electrical stimulation. High-s peed optical imaging was implemented using voltage-sensitive dyes in guinea pig visual and somatosensory cortex slices concomitantly with intracellula r recordings. Single white-matter electrical stimuli activated well-defined cortical sites with a radially oriented columnar configuration. This confi guration was followed, over the next few milliseconds, by a lateral spread of excitation through cortical layers 5 and 6 and layers 2 and 3. Much of t he optical response was eliminated in low extracellular calcium, indicating that it was primarily synaptically mediated. Repetitive stimuli at 10 Hz reproduced the spatiotemporal pattern observed for single stimuli. In contrast, repetitive stimulation in the gamma freque ncy range (similar to 40 Hz) rapidly restrained the area of excitation to a small columnar site directly above the stimulating electrode. Intracellula r recordings from cells lateral to the activated column revealed increased inhibitory synaptic activity and/or decreased excitatory responses during t he train at 40 Hz, but not during a 10 Hz stimulation. Localized microinjec tions of GABAA antagonist produced a reorganization of the geometrical acti vity pattern that was dependent on the position of the microinjection site. These findings indicate that the frequency-dependent spatial organization of neocortex activation is determined by inhibitory sculpting attributable to local network dynamics.