This proposed research program is concerned with the reorganization of neuronal networks in the brain of the adult primate following lesions that remove a major afferent system that terminates in a particular region of the brain, or in normal animals learning a sensory discrimination task. Deafferentation injuries to the human nervous system are common occurrences, often resulting in altered sensation, such as chronic pain, or in impaired movement. However, little is known about the changes in neurons or neuronal circuits as a consequence of such injuries. Our studies of reorganization of the nervous system following deafferentation will focus on two major regions of the macaque brain: the somatosensory thalamus (VPL) and the red nucleus (RN). We have shown that the two major afferent systems to VPL, the spinothalamic tract (STT) that carries pain information, and the medial lemniscus (ML) that carries nonnoxious stimuli, have fundamentally different synaptic relationships with thalamic neurons, particularly inhibitory interneurons of the thalamus. Similarly, we have shown that projections to the red nucleus from the cerebral cortex to RN have extensive interactions with interneurons of RN, but those from the cerebellum do not. We hypothesize that removal of one afferent system to VPL or to RN results in reorganization of the remaining system to form abnormal synaptic relationships that can impair the proper functioning of these major regions of the sensory and motor systems. We also suggest that deafferentation of the RN will lead ~o altered projections from the RN to its major target, the inferior olivary complex of the medulla. A knowledge of the nature of changes in neuronal circuits is essential for the design of rational therapies to treat humans with chronic brain injury. The macaque is an excellent model for seeking to understand the human sensory and motor systems, because these systems appear to be very similar in these two species. By combining studies of two systems, we can reduce the total numbers of macaques needed to investigate these two systems by carrying out parallel studies of both systems in the same animals. The studies of changes in the brain during learning will be performed in owl monkeys that have learned to discriminate the differences in timing and location of cutaneous stimuli. Such learning has been shown to result in substantial changes in the representation within the brain of the trained limbs and we will determine whether there are expanded interconnections between zones of the cerebral cortex and between cortex and the thalamus as a result of this training.
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