State-dependent auditory evoked hemodynamic responses recorded optically with indwelling photodiodes.

Implantable optical technologies provide measurements of cerebral hemodynamic activity from freely behaving animals without movement constraint or anesthesia. In order to study state-dependent neural evoked responses and the consequential hemodynamic response, we simultaneously measured EEG and scattered light changes in chronically implanted rats. Recordings took place under freely behaving conditions, allowing us to compare the evoked responses across wake, sleep, and anesthetized states. The largest evoked electrical and optical responses occurred during quiet sleep compared to wake and REM sleep, while isoflurane anesthesia showed a large, late burst of electrical activity synchronized to the stimulus but an earlier optical response.

Conditioned lick behavior and evoked responses using whisker twitches in head restrained rats.

To examine whisker barrel evoked response potentials in chronically implanted rats during behavioral learning with very fast response times, rats must be calm while immobilized with their head restrained. We quantified their behaviors during training with an ethogram and measured each individual animals' progress over the training period. Once calm under restraint, rats were conditioned to differentiate between a reward and control whisker twitch, then provide a lick response when presented with the correct stimulus, rewarded by a drop of water. Rats produced the correct licking response (after reward whisker twitch), and learned not to lick after a control whisker was twitched. By implementing a high-density 64-channel electrocorticogram (ECoG) electrode array, we mapped the barrel field of the somatosensory cortex with high spatial and temporal resolution during conditioned lick behaviors. In agreement with previous reports, we observe a larger evoked response after training, probably related to mechanisms of cortical plasticity.

Discrimination of auditory stimuli during isoflurane anesthesia.

Deep isoflurane anesthesia initiates a burst suppression pattern in which high-amplitude bursts are preceded by periods of nearly silent electroencephalogram. The burst suppression ratio (BSR) is the percentage of suppression (silent electroencephalogram) during the burst suppression pattern and is one parameter used to assess anesthesia depth. We investigated cortical burst activity in rats in response to different auditory stimuli presented during the burst suppression state. We noted a rapid appearance of bursts and a significant decrease in the BSR during stimulation. The BSR changes were distinctive for the different stimuli applied, and the BSR decreased significantly more when stimulated with a voice familiar to the rat as compared with an unfamiliar voice. These results show that the cortex can show differential sensory responses during deep isoflurane anesthesia.

Evoked response potential markers for anesthetic and behavioral states.

The rodent whisker sensory system is a commonly used model of cortical processing; however, anesthetics cause profound differences in the shape and timing of evoked responses. Evoked response studies, especially those that use spatial mapping techniques, such as fMRI or optical imaging, will thus show significantly different results depending on the anesthesia used. To describe the effect of behavioral states and commonly used anesthetics, we characterized the early surface-evoked response potentials (ERPs) components (first ERP peak: gamma band 25-45 Hz; fast oscillation: 200-400 Hz; and very fast oscillation: 400-600 Hz) using a 25-channel electrode array on the somatosensory cortex during whisker stimulation. We found significant differences in the ERP shape when ketamine/xylazine, urethane, propofol, isoflurane, and pentobarbital sodium were administered and during sleep and wake states. The highest ERP amplitudes were observed under propofol anesthesia and during quiet sleep. Under isoflurane, the ERP was nearly absent, except for a very late component, which was concombinant with burst synchronization. The slowest responses were seen under urethane and propofol anesthesia. Spatial mapping experiments that use electrical, NMR, or optical techniques must consider the anesthetic dependency of these signals, especially when stimulation protocols or electrical and metabolic responses are compared.