The proposed research is designed to extend current information about the mechanisms responsible for encoding the frequency and amplitude of vibrotactile stimuli. Although vibrotaction has been the subject of numerous psychophysical and neurophysiological investigations, and specific hypotheses were advanced twenty years ago by LaMotte and Mountcastle as to the cortical population codes for vibrotactile stimulus frequency and amplitude, no study to date has directly imaged either the global primary somatosensory cortical response to vibrotactile stimulation, or the effect of that response on its response to subsequent input drive. Nor has the global pattern of somatosensory cortical response been related effectively to the behavior of its individual neurons. In the proposed research these objectives will be met by using four types of recordings made in cats and stimulus conditions known to produce vibrotactile adaptation in humans. In each experiment the impact of preceding activity on the global pattern of response of SI forepaw cortex to a controlled vibrotactile stimulus will first be characterized at high temporal and spatial resolution using near-infrared (IR; reflectance at 730 850 nm) optical imaging of intrinsic signals. Microelectrode penetrations will then be carried out within salient regions of the overall IR activity pattern. The microelectrode penetrations will provide samples of both (i) stimulus-evoked and spontaneous spike discharge activity recorded extracellularly from single neurons, and (ii) local field potentials (LFPs) reflecting the summated activity of small neuronal aggregates. To detect and control for possible contributions by stimulus-related changes in the responsivity of skin mechanoreceptive afferents (MRAs), concurrent recordings of the stimulus-evoked MRA volley will be carried out. Analysis of the recorded neuroelectrical data will employ a variety of novel procedures designed to facilitate measurement of the well-known entrainment of neural activity associated with rhythmic skin stimuli. The applicants' preliminary studies have demonstrated that the novel procedures to be used yield useful single trial measures of the coding of vibrotactile stimulus parameters by both single SI neurons and the MRA population. Following characterization of the time-dependencies of the cortical IR and SU responses, and of the MRA population to conditions of vibrotactile stimulation known to be associated with perceptual adaptation in humans, they will investigate the effects on those time dependencies of intravenous or topical administration of drugs known to modify glutaminergic neurotransmission via selective actions on NMDA receptors (ketamine, phencyclidine, and AP-5). All experimental findings will be assessed in terms of their consistency with the applicants' working model of stimulus-evoked, NMDA receptor-dependent, corticocortical interactions within somatosensory cortex - a model which incorporates connectional details and incorporate neurotransmitter mechanisms common to all regions of neocortex. The research is anticipated to lead directly to improved understanding of the mechanisms of vibrotactile stimulus coding in SI, and in the longer term to help elucidate the cortical mechanisms involved in conditions as diverse as schizophrenia and various forms of substance abuse.
