Absence of functional FMRP causes Fragile X syndrome. Abnormalities in synaptic processes in the cerebral cortex and hippocampus contribute to cognitive deficits in Fragile X patients. So far, the potential roles of cerebellar deficits have not been investigated. Here, we demonstrate that both global and Purkinje cell-specific knockouts of Fmr1 show deficits in classical delay eye-blink conditioning in that the percentage of conditioned responses as well as their peak amplitude and peak velocity are reduced. Purkinje cells of these mice show elongated spines and enhanced LTD induction at the parallel fiber synapses that innervate these spines. Moreover, Fragile X patients display the same cerebellar deficits in eye-blink conditioning as the mutant mice. These data indicate that a lack of FMRP leads to cerebellar deficits at both the cellular and behavioral levels and raise the possibility that cerebellar dysfunctions can contribute to motor learning deficits in Fragile X patients.

The kinematics and neurophysiological aspects of eyelid movements were examined during spontaneous, voluntary, air puff, and electrically induced blinking in healthy human subjects, using the direct magnetic search coil technique simultaneously with electromyographic recording of the orbicularis oculi muscles (OO-EMG). For OO-EMG recordings, surface electrodes were attached to the lower eyelids. To measure the vertical lid displacement, a search coil with a diameter of 3 mm was placed 1 mm from the rim on the upper eyelid on a marked position. Blink registrations were performed from the zero position and from 28 randomly chosen positions. Blinks elicited by electrical stimulation of the supraorbital nerve had shortest duration and were least variable. In contrast, spontaneous blinks had longer duration and greater variability. Blinks induced by air puff had a slightly longer duration and similar variability as electrically induced blinks. There was a correlation between the maximal down phase amplitude and the integrated OO-EMG. Blink duration and maximal down phase amplitude were affected by eye position. Eyes positioned 30 degrees above horizontal displayed the shortest down phase duration and the largest maximal down phase amplitude and velocity. At 30 degrees below horizontal, blinks had the longest total duration, the longest down phase duration, and the lowest maximal down phase amplitude and velocity. The simultaneously recorded integrated OO-EMG was largest in the 30 degrees downward position. In four subjects, the average blinking data showed a linear relation between eye position and OO-EMG, maximal down phase amplitude, and maximal downward velocity.

We examined eyelid movements during spontaneous, voluntary, and trigeminal reflex blinks in 16 patients with mild to moderate Parkinson's disease (PD) off medication and 14 controls. Voluntary and reflex blink amplitudes tended to be smaller than normal for PD patients, whereas eyelid kinematics (amplitude-maximum velocity relationship) for all three blink types were normal. Spontaneous blink rate was less than normal for 10 patients and abnormally high for 6 patients. A significant positive correlation between spontaneous blink amplitude and blink rate was found. These observations suggest that PD modifies the gain of a premotor blink circuit shared by spontaneous, voluntary, and reflex blinks.

In the cynomolgus monkey, motoneurons innervating the levator palpebrae superioris muscle form a nucleus within the oculomotor nuclei called the central caudal nucleus. After double fluorescent neuronal retrograde tracing experiments, using fast blue and diamidino yellow as tracers in the levator palpebrae superior muscles, labelled motoneurons (30%) were found in an unpaired central caudal nucleus. Approximately 2% of the labelled motoneurons were double-labelled. The labelled and double-labelled neurons were distributed randomly over the central caudal nucleus, lateralization of populations of levator motoneurons within this nucleus was not observed. The afferent innervation of the levator palpebrae superioris muscle was restricted to the ophthalmic branch area of the gasserian ganglion. Primary afferent labelled neurons were absent from the mesencephalic nucleus of the fifth nerve. Surprisingly, fast blue was also found in the ophthalmic branch area of the contralateral ganglion of Gasser, while diamidino yellow was present only ipsilaterally. About 1% of the afferent labelled neurons were double-labelled. The results reveal that in the cynomolgus monkey the central caudal nucleus is not only topographically but also functionally one nucleus. Afferent innervation of the levator palpebrae superioris muscle is probably bilaterally organized.