The proposed research attempts to identify synaptic mechanisms which may account for two different forms of oculomotor plasticity which are: 1) """"""""vestibular compensation"""""""" a reduction in nystagmus induced by a unilateral labyrinthectomy, and 2) """"""""Negative optokinetic after-nystagmus""""""""- the persistence of nystagmus induced by long-term optokinetic stimulation. The possible contributions to these different forms of plasticity by two, transmitter-defined, afferent cerebellar pathways: 1) A secondary vestibular cholinergic mossy fiber pathway, and 2) A visual-vestibular climbing fiber pathway which contains the neuropeptide, corticotropin releasing factor (CRF) are examined. Extracellular single unit recordings will be made from lobule 9d (uvula) and lobule lOa (nodulus), across the mediolateral extent of these lobules. The responses of purkinje cells to naturally modulated visual and vestibular simulation will be examined in normal rabbits and in hemilabyrinthectomized rabbits. The distribution of primary vestibular mossy fiber terminals to the uvula-nodulus will be mapped using WGA-HRP as an orthograde tracer and ChAT as a double label. The influence of chemical lesions of the uvula-nodulus on vestibular decompensation will be studied. The influence of microlesions of the dorsal cap of the inferior olive on the induction of negative optokinetic afternystagmus will be measured. We will examine the distribution of ChAT in lobules 9d and lOa in normal and hemilabyrinthectomized rabbits. We will try to characterize the cerebellar muscarinic receptor using both radioligand binding and receptor autoradiography, in both normal and hemilabyrinthectomized rabbits. Extracellular and intracellular recordings from granule cells in a cerebellar slice will be attempted in order to examine the receptor action of acetylcholine on these neurons. The influence of optokinetic stimulation on the induction of increased levels of CRF mRNA in the dorsal cap of the inferior olive will be studied. The time course of this effect and the decay of CRF mRNA in the absence of stimulation will be measured. Using a cerebellar slice preparation, we will voltage clamp purkinje cells in order to study the postsynaptic action of CRF on purkinje cells. Possible optokinetically induced increases in expression of CRF in olivary neurons and climbing fiber terminals will be examined immunohistochemically.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Visual Sciences B Study Section (VISB)
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Good Samaritan Hosp & Medical Center(Prtlnd,OR)
United States
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Qian, Zuyuan; Bilderback, Timothy R; Barmack, Neal H (2008) Acyl coenzyme A-binding protein (ACBP) is phosphorylated and secreted by retinal Muller astrocytes following protein kinase C activation. J Neurochem 105:1287-99
Voogd, Jan; Barmack, Neal H (2006) Oculomotor cerebellum. Prog Brain Res 151:231-68
Barmack, Neal H; Bilderback, Timothy R; Liu, Henry et al. (2004) Activity-dependent expression of acyl-coenzyme a-binding protein in retinal muller glial cells evoked by optokinetic stimulation. J Neurosci 24:1023-33
Barmack, Neal H; Yakhnitsa, Vadim (2003) Cerebellar climbing fibers modulate simple spikes in Purkinje cells. J Neurosci 23:7904-16
Barmack, Neal H; Yakhnitsa, Vadim (2002) Vestibularly evoked climbing-fiber responses modulate simple spikes in rabbit cerebellar Purkinje neurons. Ann N Y Acad Sci 978:237-54
Barmack, N H; Qian, Z (2002) Activity-dependent expression of calbindin in rabbit floccular Purkinje cells modulated by optokinetic stimulation. Neuroscience 113:235-50
Barmack, N H; Errico, P; Ferraresi, A et al. (2002) Cerebellar nodulectomy impairs spatial memory of vestibular and optokinetic stimulation in rabbits. J Neurophysiol 87:962-75
Barmack, N H; Yakhnitsa, V (2000) Vestibular signals in the parasolitary nucleus. J Neurophysiol 83:3559-69
Barmack, N H; Fredette, B J; Mugnaini, E (1998) Parasolitary nucleus: a source of GABAergic vestibular information to the inferior olive of rat and rabbit. J Comp Neurol 392:352-72
Fushiki, H; Barmack, N H (1997) Topography and reciprocal activity of cerebellar Purkinje cells in the uvula-nodulus modulated by vestibular stimulation. J Neurophysiol 78:3083-94

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