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The Journal of Neuroscience, August 27, 2003, 23(21):7904-7916
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Cerebellar Climbing Fibers Modulate Simple Spikes in Purkinje Cells
Neal H. Barmack and
Vadim Yakhnitsa
Neurological Sciences Institute, Oregon Health and Science University,
Beaverton, Oregon 97006
Purkinje cells have two action potentials: Climbing fiber responses (CFRs)
and simple spikes (SSs). CFRs reflect the discharge of a single climbing fiber
at multiple synaptic sites on the proximal dendrite of the Purkinje cell. SSs
reflect the summed action of a subset of parallel fiber synapses on Purkinje
cell dendritic spines. Because mossy fiber afferents terminate on granule
cells, the ascending axons of which bifurcate, giving rise to parallel fibers,
the modulation of SSs has been attributed to mossy fiber afferent signals.
This inference has never been tested. Conversely, the low discharge frequency
of CFRs has led many to conclude that they have a unique and intermittent role
in cerebellar signal processing. We examine the relative potency of
vestibularly modulated mossy fiber and climbing fiber signals in evoking CFRs
and SSs in Purkinje cells of the uvula-nodulus in
chloralose-urethane-anesthetized rabbits. Vestibular primary afferents were
blocked by unilateral labyrinthectomy (UL). A UL destroys the vestibular
primary afferent signal to the ipsilateral uvula-nodulus, while leaving intact
the vestibular climbing fiber signal from the contralateral inferior olive.
After UL, vestibular stimulation modulated CFRs and SSs in ipsilateral
uvula-nodular Purkinje cells, demonstrating that the primary vestibular
afferent mossy fiber input to the ipsilateral uvula-nodulus was not necessary
for SS modulation. Unilateral microlesions of the caudal half of the
-nucleus of the inferior olive reduced a modulated climbing fiber signal
to the contralateral uvula-nodulus, causing loss of both vestibularly
modulated CFRs and SSs in contralateral Purkinje cells. Vestibular climbing
fibers not only evoke low-frequency CFRs, but also indirectly modulate
higher-frequency SSs. This modulation must be attributed to cerebellar
interneurons. Golgi cell inhibition of granule cells may provide the
interneuronal mechanism for CFR-induced SS modulation.
Key words: cerebellum; nodulus; uvula; vestibular primary afferents; parallel fiber; climbing fiber response; Golgi cell
Received Dec 27, 2002;
revised June 18, 2003;
accepted July 8, 2003.
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