Determination and quantification of pharmacological, physiological, or behavioral manipulations on ensembles of simultaneously recorded neurons in functionally related neural circuits.

The present report describes methods for evaluating the impact of physiological, pharmacological or behavioral manipulations on simultaneously recorded single neurons within a functional sensory network of the awake, freely moving rat. Surgical techniques were developed to implant a subcutaneous electrode at the base of a single facial whisker (mystacial vibrissae) so that uniform electrical stimuli could be routinely delivered to a discrete region of the whisker pad in the awake and freely moving animal. Multi-channel extracellular recording was used to monitor the spike train activity from ensembles of single neurons in whisker-related regions of the thalamus and neocortex. Algorithms were developed to verify the stability of individual cell recordings during extended experimental sessions. Additional analysis procedures and criteria were established for identifying and evaluating the treatment-specific changes in single neuron discharge patterns that are likely to occur under these experimental conditions. Finally, analyses for evaluating the impact of experimental manipulations on sensory representations distributed over populations of neurons are discussed. The development of these techniques has provided us with the means to investigate the influence of systemically administered drugs or broadly projecting monoamine pathways on single neurons and local circuits within primary sensory networks of the awake or anesthetized mammalian brain.