Voluntary reaching movements of the hand directed to a target in space under visual control involves a well-orchestrated cooperative effort on the part of several aggregates of neurons in the brain and spinal cord. Disruption of these circuits as a result of brain trauma, stroke or tumor, leads to a severe deficit in the ability to effectively use the hands and fingers. Included among the circuits that participate in the control of such movements is the cortico-ponto-cerebellar system. The basilar pontine nuclei (BPN) represent an important intermediate between the cerebral cortex and cerebellum and the literature indicates that nearly all functional subdivisions of the cortex project to the pontine gray, and in turn, the BPN project to widespread areas of the cerebellum, including the cerebellar nuclei. Recently this laboratory has provided considerable evidence supporting the notion that the pontine gray is much more of an integrative center than was formerly recognized. Such evidence includes: 1)the existence of GABA-immunoreactive local circuit neurons that appear to form presynaptic dendritic elements in the BPN, 2)an extremely diverse array of afferent projections to the BPN including somatosensory input from the periphery, and 3)the presence of convergent input to single BPN neurons from more than one afferent system. Despite this recently accumulated body of information, much remains to be learned about the precise details of synaptic circuitry and perhaps more importantly, the functional role of the BPN. The proposed experiments seek to extend to the monkey a series of studies initiated in the rodent concerning the presence and synaptic relations of putative inhibitory interneurons in the BPN. Based upon preliminary observations in the monkey it has become quite dear that the relative number of GABA neurons is significantly higher in the monkey BPN than in rat. Equally important, however, is the abundance of complex synaptic arrangements that exist in the monkey BPN. We anticipate therefore, that anatomical studies of synaptic relations in the BPN will be far more productive in monkey and studies are proposed to identify projection zones and synaptic boutons of three important BPN afferent systems arising in the cerebellar nuclei, dorsal column nuclei and zona incerta. In addition, the participation of these afferent systems in glomerular synaptic complexes along with BPN projection neuron dendrites will be determined in experiments involving retrograde labeling of projection neurons from cerebellar injections. Once these synaptic circuits are better understood, physiological studies will be initiated using the incertopontine system. The Co-P.I. has a great deal of experience recording zona incerta neurons in an awake, behaving monkey trained to make a variety of specific eye movements. By recording in the BPN in the same animal and by knowing the detailed anatomy of incertopontine axons and terminals and their relations with BPN projection and local circuit neurons, it should be possible to begin an in depth exploration of the functional activity of BPN neurons.

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National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology A Study Section (NEUA)
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University of Mississippi Medical Center
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Lee, H S; Mihailoff, G A (1999) Fluorescent double-label study of lateral reticular nucleus projections to the spinal cord and periaqueductal gray in the rat. Anat Rec 256:91-8
Liu, H; Mihailoff, G A (1999) Hypothalamopontine projections in the rat: anterograde axonal transport studies utilizing light and electron microscopy. Anat Rec 255:428-51
Mihailoff, G A (1995) Orthograde axonal transport studies of projections from the zona incerta and pretectum to the basilar pontine nuclei in the rat. J Comp Neurol 360:301-18
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