We propose three areas of investigation to understand how the circuitry of the vestibulocerebellum uses vestibular information to modify the simple spike (SS) output of Purkinje cells and how this output contributes to behavioral adaptation to altered vestibular orientation: 1) Circuitry transmitting vestibular information to inferior olive. The parasolitary nucleus (Psol) conveys vestibular signals to the beta-nucleus and dorsomedial cell column (dmcc), two subnuclei of the inferior olive. Unilateral lesions of Psol reduce, but do not eliminate vestibularly-modulated climbing fiber responses (CFRs) in the contralateral uvula-nodulus, implying an alternative presynaptic vestibular pathway to the inferior olive. The Y-group may be the origin of this alternative pathway. We will combine retrograde and orthograde tracers with recordings from single Y-group neurons to determine the types of vestibular and optokinetic signals carried by them. 2) Conjunctive CFR-SS vestibular plasticity in the nodulus, understanding interactions between climbing and parallel fibers on Purkinje cells is critical to understanding the cerebellum. Interactions occur with short- or long-term consequences. We will electrically stimulate parallel and climbing fibers in vivo so that their interactions can be interpreted in terms of known vestibular circuitry. A climbing fiber volley from a known semicircular canal zone in the beta-nucleus, will be interacted with a parallel fiber volley from a single vertical semicircular canal. These interactions should reveal how climbing fiber topography is reflected in Purkinje cell output. 3) Behavioral evaluation of the role of the uvula-nodulus in the dynamic control of vestibule-ocular reflex orientation in space. Rotation of rabbits about a longitudinal axis modulates the velocity and orientation of a previously induced optokinetic afternystagmus (OKAN II). The significance of decreases in nystagmus velocity and the possible contribution of the nodulus to modification of eye velocity are poorly understood. We suggest that head tilt induces a reduction in nystagmus velocity to reduce the gain of all eye reflexes that conflict perceived vertical orientation or a previously """"""""remembered"""""""" orientation. We will measure changes in slow phase velocity when the orientation of the rabbit's head causes nystagmus to be executed at different angles within the orbit before and after bilateral destruction of the uvula-nodulus.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
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Sensorimotor Integration Study Section (SMI)
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Platt, Christopher
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Oregon Health and Science University
Schools of Medicine
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Barmack, N H; Yakhnitsa, V (2015) Climbing fibers mediate vestibular modulation of both ""complex"" and ""simple spikes"" in Purkinje cells. Cerebellum 14:597-612
Barmack, N H; Yakhnitsa, V (2013) Modulated discharge of Purkinje and stellate cells persists after unilateral loss of vestibular primary afferent mossy fibers in mice. J Neurophysiol 110:2257-74
Qian, Z; Micorescu, M; Yakhnitsa, V et al. (2012) Climbing fiber activity reduces 14-3-3-? regulated GABA(A) receptor phosphorylation in cerebellar Purkinje cells. Neuroscience 201:34-45
Qian, Zuyuan; Yakhnitsa, Vadim; Barmack, Neal H (2011) Climbing fiber-evoked Purkinje cell discharge reduces expression of GABA(A) receptor-associated protein and decreases its interaction with GABA(A) receptors. J Neurochem 117:197-208
Barmack, Neal H; Yakhnitsa, Vadim (2011) Microlesions of the inferior olive reduce vestibular modulation of Purkinje cell complex and simple spikes in mouse cerebellum. J Neurosci 31:9824-35
Pettorossi, V E; Ferraresi, A; Botti, F M et al. (2011) Head position modulates optokinetic nystagmus. Exp Brain Res 213:141-52
Barmack, Neal H; Yakhnitsa, Vadim (2011) Topsy turvy: functions of climbing and mossy fibers in the vestibulo-cerebellum. Neuroscientist 17:221-36
Barmack, N H; Qian, Z; Yakhnitsa, V (2010) Climbing fibers induce microRNA transcription in cerebellar Purkinje cells. Neuroscience 171:655-65
Barmack, N H; Yakhnitsa, V (2008) Distribution of granule cells projecting to focal Purkinje cells in mouse uvula-nodulus. Neuroscience 156:216-21
Barmack, Neal H; Yakhnitsa, Vadim (2008) Functions of interneurons in mouse cerebellum. J Neurosci 28:1140-52

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