Climbing Fibers Mediate Vestibular Modulation of Both “Complex” and “Simple Spikes” in Purkinje Cells

Abstract

Climbing and mossy fibers comprise two distinct afferent paths to the cerebellum. Climbing fibers directly evoke a large multispiked action potential in Purkinje cells termed a "complex spike" (CS). By logical exclusion, the other class of Purkinje cell action potential, termed "simple spike" (SS), has often been attributed to activity conveyed by mossy fibers and relayed to Purkinje cells through granule cells. Here, we investigate the relative importance of climbing and mossy fiber pathways in modulating neuronal activity by recording extracellularly from Purkinje cells, as well as from mossy fiber terminals and interneurons in folia 8-10. Sinusoidal roll-tilt vestibular stimulation vigorously modulates the discharge of climbing and mossy fiber afferents, Purkinje cells, and interneurons in folia 9-10 in anesthetized mice. Roll-tilt onto the side ipsilateral to the recording site increases the discharge of both climbing fibers (CSs) and mossy fibers. However, the discharges of SSs decrease during ipsilateral roll-tilt. Unilateral microlesions of the beta nucleus (β-nucleus) of the inferior olive blocks vestibular modulation of both CSs and SSs in contralateral Purkinje cells. The blockage of SSs occurs even though primary and secondary vestibular mossy fibers remain intact. When mossy fiber afferents are damaged by a unilateral labyrinthectomy (UL), vestibular modulation of SSs in Purkinje cells ipsilateral to the UL remains intact. Two inhibitory interneurons, Golgi and stellate cells, could potentially contribute to climbing fiber-induced modulation of SSs. However, during sinusoidal roll-tilt, only stellate cells discharge appropriately out of phase with the discharge of SSs. Golgi cells discharge in phase with SSs. When the vestibularly modulated discharge is blocked by a microlesion of the inferior olive, the modulated discharge of CSs and SSs is also blocked. When the vestibular mossy fiber pathway is destroyed, vestibular modulation of ipsilateral CSs and SSs persists. We conclude that climbing fibers are primarily responsible for the vestibularly modulated discharge of both CSs and SSs. Modulation of the discharge of SSs is likely caused by climbing fiber-evoked stellate cell inhibition.

Repeated inhalation of sevoflurane inhibits the information transmission of Purkinje cells and delays motor development via the GABAA receptor ε subunit in neonatal mice

“…In the afferent fibers of the cerebellum, climbing fibers and mossy fibers may combine with PC dendrites to form excitatory synaptic connections ( 18 ). Excitatory afferents of climbing fibers may cause PC excitability, characterized by complex spikes and, subsequent to the formation of synaptic connection between the mossy fibers and granular cells, PC excitability is indirectly excited through the axons of granulosa cells and parallel fibers, and manifests as simple spikes ( 6 , 18 ). Basket cells (BCs) stellate cells (SCs) are the inhibitory interneurons of PCs; the long axon terminals of BCs are wrapped in the soma and axon segments of 3–5 PCs ( 19 ).…”

“…The cerebellum is an important motor center; once the external information is precision computed and synthesized, a variety of output instructions are issued by Purkinje cells (PCs) to facilitate the completion of numerous physiological activities ( 5 , 6 ). PCs, the only output neuron in the cerebellar cortex, are highly sensitive to narcotics ( 6 ). Repeated anesthesia may lead to PC degeneration, dendritic cell reduction and cerebellar degeneration in children ( 7 ).…”

A narrative review of the impact of cerebellar dysfunction and sleep disturbances after general anesthesia in patients with Alzheimer’s disease

“…Motor cerebellar lesions can cause movement disorders, but cognitive and limbic cerebellar lesions in the posterior lobe can cause intellectual and emotional sensory disorders (cerebellar affective syndrome) (1). Purkinje cells (PC) are the only output neurons in the cerebellar cortex and are highly sensitive to anesthetics (21). Repeated anesthesia may cause PC degeneration, dendritic cell reduction and cerebellar degeneration (22).…”

Editorial on the Honorary Cerebellum Issue for the Retirement of Enrico Mugnaini

“…He did excellent work on a great variety of topics, many of which were related to the distribution and projections of GABAergic neurons [1], the cyto-architecture of various parts of the nervous system, in particular the auditory system [2,3] and the cerebellum [4], culminating in the work on the morphology and function of unipolar brush cells (UBCs) [5]. The variety of these topics is also reflected in the contributions of Enrico's colleagues and friends in the current issue for The Cerebellum: four papers largely focused on the development, electrophysiology, or systems function of GABAergic neurons [6][7][8][9], five papers on the structure and function of UBCs [10][11][12][13][14], while the remaining papers addressed either hyperplastic and degenerative aspects of cerebellar pathology [15,16], or the interregional connectivity within the auditory system [17,18]. The formats range from those of commentaries or opinion papers to those of extensive reviews or original articles.…”

“…1 Picture of Enrico Mugnaini, taken at the Lake of Chicago in August 2013, courtesy of Marco Martina cortex look like in the whole-cell in vivo preparation [7]. Next, Neal Barmack, another collaborator of Enrico at UCONN, provides his opinion on data indicating that modulation of interneurons in the vestibulocerebellum can, to a large extent, be determined by activity in the climbing fibers originating in the inferior olive [8], while Piergiorgio Strata, one of the major colleagues from his home country, Italy, outlines the literature addressing the issue as to what extent the cerebellum and its inhibitory connections might also play a role in emotional responses [9].…”