Craig Evinger

An Explanation for Reflex Blink Hyperexcitability in Parkinson’s Disease. I. Superior Colliculus

Hyperexcitable reflex blinks are a cardinal sign of Parkinson’s disease. We investigated the neural circuit through which a loss of dopamine in the substantia nigra pars compacta (SNc) leads to increased reflex blink excitability. Through its inhibitory inputs to the thalamus, the basal ganglia could modulate the brainstem reflex blink circuits via descending cortical projections. Alternatively, with its inhibitory input to the superior colliculus, the basal ganglia could regulate brainstem reflex blink circuits via tecto-reticular projections. Our study demonstrated that the basal ganglia utilizes its GABAergic input to the superior colliculus to modulate reflex blinks. In rats with previous unilateral 6-hydroxydopamine (6-OHDA) lesions of the dopamine neurons of the SNc, we found that microinjections of bicuculline, a GABA antagonist, into the superior colliculus of both alert and anesthetized rats eliminated the reflex blink hyperexcitability associated with dopamine depletion. In normal, alert rats, decreasing the basal ganglia output to the superior colliculus by injecting muscimol, a GABA agonist, into the substantia nigra pars reticulata (SNr) markedly reduced blink amplitude. Finally, brief trains of microstimulation to the superior colliculusreduced blink amplitude. Histological analysis revealed that effective muscimol microinjection and microstimulation sites in the superior colliculus overlapped the nigro-tectal projection from the basal ganglia. These data support models of Parkinsonian symtomatology that rely on changes in the inhibitory drive from basal ganglia output structures. Moreover, they support a model of Parkinsonian reflex blink hyperexcitability in which the SNr–SC target projection is critical.

Head Orientation in Pigeons: Postural, Locomotor and Visual Determinants

We have determined the pigeons head orientation for two postures and two locomotor activities that do not involve a specific visual stimulus. Using a high-speed cine camera, we filmed four pigeons (Columba livia) while (1) flying, (2) walking, (3) perching and (4) standing on a flat surface. Under these conditions, the head orientation is relatively constant, allowing us to estimate the normal horizon of the visual field and thus the horizontal meridian of the retina. Measurements of the lateral semicircular canal showed that the canal is tilted slightly up with respect to the horizon in the head orientation determined by the film analysis. In contrast to their relatively stable head posture during locomotion, the pigeons consistently altered their head orientation when presented with seed targets, apparently to fixate each seed with a small portion of the visual field around the bill tip.

Anatomy and physiology of intracellularly labelled omnipause neurons in the cat and squirrel monkey

SummarySaccadic omnipause neurons (OPNs) were intracellularly labelled with horseradish peroxidase (HRP) in alert cats and squirrel monkeys. The somas of OPNs were located on or near the midline in the caudal pons and their axons projected to regions of the pontomedullary reticular formation that contain the excitatory and inhibitory burst neurons.

Update on blepharospasm: report from the BEBRF International Workshop.

This review updates understanding and research on blepharospasm, a subtype of focal dystonia. Topics covered include clinical aspects, pathology, pathophysiology, animal models, dry eye, photophobia, epidemiology, genetics, and treatment. Blepharospasm should be differentiated from apraxia of eyelid opening. New insights into pathology and pathophysiology are derived from different types of imaging, including magnetic resonance studies. Physiologic studies indicate increased plasticity and trigeminal sensitization. While botulinum neurotoxin injections are the mainstay of therapy, other therapies are on the horizon.

Not looking while leaping: the linkage of blinking and saccadic gaze shifts

Many vertebrates generate blinks as a component of saccadic gaze shifts. We investigated the nature of this linkage between saccades and blinking in normal humans. Activation of the orbicularis oculi, the lid closing muscle, EMG occurred with 97% of saccadic gaze shifts larger than 33°. The blinks typically began simultaneously with the initiation of head and/or eye movement. To minimize the possibility that the blinks accompanying saccadic gaze shifts were reflex blinks evoked by the wind rushing across the cornea and eyelashes as the head and eyes turned, the subjects made saccadic head turns with their eyes closed. In this condition, orbicularis oculi EMG activity occurred with all head turns greater than 17° in amplitude and the EMG activity began an average of 39.3 ms before the start of the head movement. Thus, one component of the command for large saccadic gaze shifts appears to be a blink. We call these blinks gaze-evoked blinks. The linkage between saccadic gaze shifts and blinking is reciprocal. Evoking a reflex blink prior to initiating a voluntary saccadic gaze shift dramatically reduces the latency of the initiation of the head movement.

Transsynaptic retrograde transport of fragment C of tetanus toxin demonstrated by immunohistochemical localization

Injection of the non-toxic fragment C of tetanus toxin into the superior oblique muscle of the eye results in strong direct retrograde labelling of the motoneurons in the contralateral trochlear nucleus and clear transsynaptic labelling of neurons in the ipsilateral and contralateral vestibular nuclei. Standard immunohistochemical procedures using a monoclonal antibody localize fragment C in the brain with high sensitivity and excellent resolution. An injection of fragment C into the superior oblique muscle labels the same pool of trochlear motoneurons as an HRP injection into the superior oblique muscle. A comparison of the fragment C labelling of trochlear motoneurons with intracellular injections of HRP into trochlear motoneurons suggests that fragment C stains not just the soma, but also the distal dendrites of motoneurons. Moreover, a fragment C injection into the superior oblique muscle labels transsynaptically more neurons in each vestibular nucleus than an injection of HRP into the trochlear nucleus labels directly.

Different forms of blinks and their two-stage control

SummaryThe purpose of this paper is to examine blink kinematics and the neural basis of blinks evoked reflexively by different kinds of stimuli. The kinematics of the upper lid movement and the electromyographic response of lid muscles levator palpebrae and orbicularis oculi were recorded in the rabbit during trigeminally and visually-evoked blinks. We find that there is a basic, kinematic difference between blinks. A blink in response to an airpuff is more rapidly accomplished and achieves a higher velocity than does an equal amplitude blink in response to a flash of light. The two forms of the reflex blink result from differences in the nature and timing of activity in antagonistic lid muscle motoneurons. Nevertheless, most characteristics of blink neural control are common to both reflex blinks. Most importantly, it appears that blinks are produced by two-stage neural control, an early component that is preprogrammed and a late component that is under stimulus control.

Midbrain 6-hydroxydopamine lesions modulate blink reflex excitability

The blink reflex abnormalities present in the 6 hydroxydopamine (6-OHDA) lesioned rat model of parkinsonism mimicked those of the human with Parkinons disease. In alert rats, we monitored the long and short latency components of the orbicularis oculi electromyographic (OOemg) response evoked by electrical stimulation of the supraorbital branch of the trigeminal nerve (SO). Two paradigms, habituation and double pulse, provided a measure of blink reflex excitability. In normal rats, repeated stimulation of the SO produced habituation of the R2 component of the blink. In the double pulse paradigm, presentation of two identical SO stimuli resulted in a reduced or suppressed OOemg response to the second stimulus relative to the first. In rats with complete, unilateral lesions of midbrain dopamine neurons, repeated SO stimulation produced facilitation rather than habituation of the R2 component of the blink reflex. This facilitation occurred only with the eyelid contralateral to the lesion. In the double pulse paradigm, the lesioned rats showed increased excitability rather than suppression. This effect occurred bilaterally, although the increased excitability was strongest contralateral to the lesion. Rats with partial lesions of midbrain dopamine neurons exhibited qualitatively similar, but less pronounced blink reflex abnormalities. The R1 component of the blink reflex was unaffected by either the complete or partial lesions. Thus, modification of the blink reflex by 6-OHDA lesions provides a reproducible parkinsonian-like symptom which is amenable to investigations of increases in reflex excitability.

A role for the basal ganglia in nicotinic modulation of the blink reflex

SummaryIn humans and rats we found that nicotine transiently modifies the blink reflex. For blinks elicited by stimulation of the supraorbital branch of the trigeminal nerve, nicotine decreased the magnitude of the orbicularis oculi electromyogram (OOemg) and increased the latency of only the long-latency (R2) component. For blinks elicited by electrical stimulation of the cornea, nicotine decreased the magnitude and increased the latency of the single component of OOemg response. Since nicotine modified only one component of the supraorbitally elicited blink reflex, nicotine must act primarily on the central nervous system rather than at the muscle. The effects of nicotine could be caused by direct action on lower brainstem interneurons or indirectly by modulating descending systems impinging on blink interneurons. Since precollicular decerebration eliminated nicotines effects on the blink reflex, nicotine must act through descending systems. Three lines of evidence suggest that nicotine affects the blink reflex through the basal ganglia by causing dopamine release in the striatum. First, stimulation of the substantia nigra mimicked the effects of nicotine on the blink reflex. Second, haloperidol, a dopamine (D2) receptor antagonist, blocked the effect of nicotine on the blink reflex. Third, apomorphine, a D2 receptor agonist, mimicked the effects of nicotine on the blink reflex.

Characterizing The Spontaneous Blink Generator: An Animal Model

Although spontaneous blinking is one of the most frequent human movements, little is known about its neural basis. We developed a rat model of spontaneous blinking to identify and better characterize the spontaneous blink generator. We monitored spontaneous blinking for 55 min periods in normal conditions and after the induction of mild dry eye or dopaminergic drug challenges. The normal spontaneous blink rate was 5.3 ± 0.3 blinks/min. Dry eye or 1 mg/kg apomorphine significantly increased and 0.1 mg/kg haloperidol significantly decreased the blink rate. Additional analyses revealed a consistent temporal organization to spontaneous blinking with a median 750 s period that was independent of the spontaneous blink rate. Dry eye and dopaminergic challenges significantly modified the regularity of the normal pattern of episodes of frequent blinking interspersed with intervals having few blinks. Dry eye and apomorphine enhanced the regularity of this pattern, whereas haloperidol reduced its regularity. The simplest explanation for our data is that the spinal trigeminal complex is a critical element in the generation of spontaneous blinks, incorporating reflex blinks from dry eye and indirect basal ganglia inputs into the blink generator. Although human subjects exhibited a higher average blink rate (17.6 ± 2.4) than rats, the temporal pattern of spontaneous blinking was qualitatively similar for both species. These data demonstrate that rats are an appropriate model for investigating the neural basis of human spontaneous blinking and suggest that the spinal trigeminal complex is a major element in the spontaneous blink generator.