Increased occurrence of climbing fiber inputs to the cerebellar flocculus in a mutant mouse is correlated with the timing delay of optokinetic response

Abstract

The cerebellum plays an essential role in motor control, and its dysfunction may delay the onset of action and disrupt smooth and efficient movement. A Purkinje neuron (PN), the sole output cell type in the cerebellar cortex, receives two distinct types of excitatory synaptic inputs, numerous weak inputs from granule neurons (GNs) and occasional strong inputs from a climbing fiber (CF). The role of each input and the significance of low firing rate of CF have been studied. Here we show that the increased occurrence of CF inputs altered the firing pattern of a PN, which was correlated with timing of a reflex. We used the mutant mice deficient in the glutamate receptor delta2 subunit, a molecule related to ionotropic glutamate receptor specifically expressed at GN-PN synapses. The mutant mouse shows more frequent CF inputs and longer timing delay in optokinetic response (OKR), reflex eye movement that follows slow motion of a large visual field. A PN shows two types of action potentials: complex spikes (CS) induced by CF inputs; and simple spikes. They changed respective firing rates during sinusoidal optokinetic stimulation, and the timing of each firing rate modulation was similar in wild-type and mutant mice. However, increased occurrence of CS in the mutant altered the total firing pattern of a PN in the flocculus, which was correlated with the timing delay of OKR. These results support the functional merit of low firing rate of CF in motor control.

Cerebellar Purkinje cell activity drives motor learning

“…We compared the average, spontaneous firing rate of each Purkinje cell during periods between trains of blue light stimulation with the average firing rate during the trains of the blue light stimulation. The trains of brief light pulses used in the behavioral experiments (50-Hz train of 5-ms pulses for 420 ms with intensity ≤ 3mW mm −2 ) achieved an increase in Purkinje cell firing rate comparable in amplitude and duration to what occurs during visual and vestibular oculomotor behaviors 27,32 (Supplementary Fig. 2).…”

Psychophysical testing in rodent models of glaucomatous optic neuropathy

“…Continuous repetition of the stimulus results in a slow tracking and fast saccadic-like resetting motion, called optokinetic nystagmus (OKN) (Cahill and Nathans, 2008; Stahl, 2004; Sugita et al, 2013). There are, in fact, two main oculomotor reflexes, the OKR and vestibule-ocular reflex (VOR), that work together to reduce retinal slip (Andreescu et al, 2005; Iwashita et al, 2001; Katoh et al, 2005; Stahl, 2004; Tanaka et al, 2013; Thomas et al, 2010; van Alphen et al, 2010; Yoshida et al, 2007) and are mainly controlled by subcortical circuits (Cahill and Nathans, 2008). The semicircular canals of the vestibular system provide an estimate of head rotation in response to head movement which elicits the VOR that generates eye movements to compensate for the head rotation (Stahl, 2004; Tanaka et al, 2013; van Alphen and De Zeeuw, 2002).…”

Hormones and the neuromuscular control of courtship in the golden-collared manakin (Manacus vitellinus)

“…The cerebellum has a crucial role in complex motor function (Paula-Barbosa and Sobrinho-Simoes, 1976; Tohyama, 1976; Paula-Barbosa et al, 1980; Smith et al, 1993; Molinari et al, 2001; Rodriguez et al, 2005; Yoshida et al, 2007) and was found to express significant AR in the golden-collared manakin. As in other vertebrates, limb movements of passeriform species activate cerebellar immediate-early gene expression (Feenders et al, 2008), and lesions of the cerebellum disturb motor and cognitive performance (Spence et al, 2009).…”