The Clinton Foundation and Global Health Governance

Abstract

Although it is evident that general anesthesia should affect impulse activity and neurochemical responses of central neurons, there are limited studies in which these parameters were compared in both awake and anesthetized animal preparations. We used single-unit recording coupled with iontophoresis to examine impulse activity and responses of substantia nigra pars reticulata (SNr) neurons to GABA, glutamate (GLU), and dopamine (DA) in rats in awake, unrestrained conditions and during chloral hydrate anesthesia. SNr neurons in both conditions had similar organization of impulse flow, but during anesthesia, they have lower mean rates and discharge variability than in awake conditions. In individual units, discharge rate in awake, quietly resting rats was almost three-fold more variable than during anesthesia. These cells in both conditions were highly sensitive to iontophoretic GABA, but the response was stronger during anesthesia. In contrast to virtually no responses to GLU in awake conditions, most SNr neurons during anesthesia were excited by GLU; the response occurred preferentially in slow-firing units, which were atypical of awake conditions. Consistent with no postsynaptic DA receptors on SNr neurons, iontophoretic DA was ineffective in altering discharge rates in awake conditions, but often induced weak excitations during anesthesia. Although SNr neurons are autoactive, generating discharges without any excitatory input (i.e., in vitro), their impulse activity and responses to natural neurochemical inputs are strongly affected by general anesthesia. Some alterations appear to be specific to the general anesthetic used, while others probably reflect changes in the activity of afferent inputs, brain metabolism and neurotransmitter uptake that are typical to any type of general anesthesia. Therefore, an awake, freely moving animal preparation appears to be advantageous for studying impulse activity and neurochemical interactions at single-neuron level during physiologically relevant conditions