Deficits in auditory processing are a characteristic of schizophrenia. These have been formally demonstrated using a sensory gating paradigm in which surface auditory evoked potentials (AEPs) are measured in response to the presentation of closely paired clicks. Schizophrenics, unlike normal controls, show little or no inhibitory gating of a midlatency wave, P50, to the second click. The synaptic pathways and neurobiological mechanisms which are responsible for normal sensory gating, or the deficit seen in schizophrenia, are not known. Further, these circuits and mechanisms cannot be investigated in human subjects, due to the invasive nature of the anatomical and physiological technique involved. While there is no animal model of schizophrenia, there is a significant amount of evidence that the hippocampus is a site of pathology in this disease. We also have preliminary evidence for a hippocampal AEP in rats, N50, which has many features in common with human P50. The purpose of this project is to determine how auditory input reaches the hippocampus and how it is gated there. The results of this work will not definitively demonstrate which neuronal mechanisms are responsible for the gating of human P50, but they will indicate possible directions for further investigation in other projects in the Center. In collaboration with Project 4, we will explore the electrophysiology of sensory gating in nonhuman primates to validate our findings in a more "advanced" brain. In collaboration with Project 5, we will isolate relevant circuits in intraocular transplants made from fetal rat tissue. This work will guide subsequent experiments in Project 5 which will involve transplantation of human fetal tissues.
NIH ExPorter
NIH ExPorter