The eyelids blink to restore the corneal tear film, clear debris from the cornea, and protect the cornea from airborne threats. The eyelids also move conjugately with vertical eye movements so as not to obscure vision. To accomplish these tasks, eyelids incorporate both skeletal and extraocular muscles, thereby creating a deep linkage of the neural circuits controlling blinking and eye movements. To compensate for corneal challenges such as dry eye, neuronal blink circuits modify themselves to increase blink excitability and develop blink oscillations. Although these compensatory modifications normally support corneal homeostasis, dysfunction of these adaptations can lead to the focal dystonia benign essential blepharospasm.

Blinking sustains the corneal tear film generated by sexually dimorphic lacrimal and meibomian glands. Our study examines whether trigeminal control of blinking is also sexually dimorphic by investigating trigeminal reflex blinking, associative blink modification, and spontaneous blinking in male and female rats before and after unilateral dry eye caused by exorbital gland removal. Before gland removal, female rats exhibited a lower threshold for evoking trigeminal reflex blinks, a weaker effect of associative blink modification, and longer-duration spontaneous blinks than males. Spontaneous blink rate, reflex blink excitability, and occurrence of blink oscillations did not differ between the sexes. Reanalysis of previous data showed that humans showed the same blink sexual dimorphisms as rats. During the first 2 wk of dry eye, trigeminal blink circuit excitability and blink oscillations steadily rose in male rats, whereas excitability and blink oscillations did not change in females. Following dry eye, spontaneous blink duration increased for both males and females, whereas spontaneous blink rate remained constant for males but decreased for females. The associative modification treatment to depress trigeminal blink amplitude initially produced blink depression in males that converted to blink potentiation as trigeminal excitability rose, whereas females exhibited progressively more blink depression. These data indicated that dry eye increased excitability in male trigeminal reflex blink circuits at the expense of circuit modifiability, whereas trigeminal modifiability increased in females. This increased modifiability of female trigeminal blink circuits with dry eye may contribute to the preponderance of females developing the focal dystonia, benign essential blepharospasm.NEW & NOTEWORTHY All the elements controlling the corneal tear film are sexually dimorphic. Blinking, which smooths and maintains the tear film, also exhibits sex differences. Dry eye increases the sexual dimorphisms of blinking, including increased exaggeration of excitability in males and enhanced modifiability of the female trigeminal complex. This increased modifiability may explain female predominance in the development of the focal dystonia, benign essential blepharospasm.

Spontaneous eye blink rate (SBR) has been associated with central dopamine (DA) levels, raising the intriguing possibility that SBR is related to cognitive functions dependent on DA, such as spatial working memory (WM). We tested this hypothesis in two behavioral experiments, examining the relationship between SBR, WM load and individual differences in spatial WM performance in 126 young adults. In Experiment 1, we examined the temporal profile of SBR during a spatial delayed recognition task requiring maintenance of 1, 2, 4, 6 or 7 dot locations. We observed a suppression in SBR during dot- and recognition probe-presentation, and a significant increase in SBR afterwards. High performers showed significantly lower SBR than low performers during the first 500 ms of the delay period. In Experiment 2, we used a similar spatial WM task as Experiment 1 to test whether an instructed voluntary blink during the early delay would directly dampen WM performance. While the temporal dynamics of SBR across task events were comparable to Experiment 1, WM performance was not significantly different between the voluntary blink and no blink conditions. Together, these results suggest that spontaneous but not voluntary eye blinking is closely linked to spatial WM, and that lower SBR during WM encoding and early phase of maintenance is associated with better WM task performance.

Parkinson's disease (PD) patients and the 6-hydroxydopamine (6-OHDA) lesioned rat model share blink abnormalities. In view of the evolutionarily conserved organization of blinking, characterization of blink reflex circuits in rodents may elucidate the neural mechanisms of PD reflex abnormalities. We examine the extent of this shared pattern of blink abnormalities by measuring blink reflex excitability, blink reflex plasticity, and spontaneous blinking in 6-OHDA lesioned rats. We also investigate whether 130-Hz subthalamic nucleus deep brain stimulation (STN DBS) affects blink abnormalities, as it does in PD patients. Like PD patients, 6-OHDA-lesioned rats exhibit reflex blink hyperexcitability, impaired blink plasticity, and a reduced spontaneous blink rate. At 130 Hz, but not 16 Hz, STN DBS eliminates reflex blink hyperexcitability and restores both short- and long-term blink plasticity. Replicating its lack of effect in PD patients, 130-Hz STN DBS does not reinstate a normal temporal pattern or rate to spontaneous blinking in 6-OHDA lesioned rats. These data show that the 6-OHDA lesioned rat is an ideal model system for investigating the neural bases of reflex abnormalities in PD and highlight the complexity of PD's effects on motor control, by showing that dopamine depletion does not affect all blink systems via the same neural mechanisms.

Effectively modeling benign essential blepharospasm (BEB) requires mimicking its root causes. Current evidence points to BEB arising from the confluence of a genetic predisposing condition and an environmental trigger (1). In this "2 hit" hypothesis, the appropriate environmental trigger engenders dystonic behavior because the predisposing condition creates inappropriate brain functioning. Epidemiological studies demonstrate that eye irritation from dry eye, blepharitis, or keratoconjunctivitis is the environmental trigger (1–61–61–61–61–61–6). The strength of the association between dry eye and BEB increases in the fifth and sixth decades of life (6) when BEB typically arises (7). Available data strongly support that the predisposing condition is genetic (1,8–121,8–121,8–121,8–121,8–121,8–12). There is evidence for an autosomal-dominant gene with reduced penetrance contributing to BEB (9,139,13), but current studies fail to identify any specific genes (8,148,14). Thus, creating a useful animal model of BEB must involve combining an environmental trigger with a predisposing condition. Another goal of an animal model is to reproduce the typical symptoms of BEB. The hallmark of BEB is excessive involuntary bilateral lid closure primarily involving the orbicularis oculi muscles (1,15–181,15–181,15–181,15–181,15–18). In addition to lid spasms, patients with BEB exhibit trigeminal hyperexcitability (1,15,19–221,15,19–221,15,19–221,15,19–221,15,19–221,15,19–22), an elevated spontaneous blink rate (23), and photophobia (1,24–261,24–261,24–261,24–26). These characteristics are consistent with eye irritation serving as the environmental trigger for BEB because they all appear in patients with dry eye (21,27,2821,27,2821,27,28). This relationship between eye irritation and BEB characteristics indicates that eye irritation should be 1 component of an animal model and that the predisposing condition should cause the adaptive changes in eyelid control in response to dry eye to develop into BEB-like characteristics. Current evidence demonstrates that trigeminal blink circuits undergo plastic, adaptive modifications to compensate for the rapid breakup of the corneal tear film in dry eye (29–3229–3229–3229–32). Dry eye or eye irritation elevates trigeminal blink amplitude and duration to increase meibomian gland secretion and enhance restoration of the tear film (20,32–3720,32–3720,32–3720,32–3720,32–3720,32–3720,32–37). Blink frequency increases to reform the tear film more regularly (20,36–4020,36–4020,36–4020,36–4020,36–4020,36–40). The trigeminal reflex blink circuit becomes hyperexcitable to allow tear film breakup to evoke a reflex blink more readily (20,21,3220,21,3220,21,32). Finally, the trigeminal reflex blink circuit responds to a single reflex evoking stimulus with multiple blinks to help restore the tear film (20,21,3220,21,3220,21,32). A simple experiment demonstrates that these modifications are part of a compensatory plastic change occurring in the trigeminal complex (32). Within 30 minutes of restraining 1 eyelid to make blinking more difficult, stimulating the supraorbital nerve ipsilateral to the restrained eyelid evokes hyperexcitable reflex blinks and additional blinks in both eyelids. Stimulating the supraorbital nerve contralateral to the restrained eyelid, however, elicits normal blinks in both eyelids. This pattern would occur only if the trigeminal complex receiving signals of corneal irritation from eyelid restraint expressed the plastic changes. Thus, eye irritation initiates plastic compensatory changes in blinking that could be exaggerated in BEB to produce the eyelid abnormalities of this focal dystonia. We hypothesize that the predisposing condition exaggerates neuroplasticity so that modifications in response to eye irritation become maladaptive and amplify into the characteristics of BEB. There is significant evidence for exaggerated plasticity in dystonia (41,4241,42). With generalized dystonia, homeostatic synaptic plasticity in the striatum is abnormal (43,4443,44). Exaggerated associative plasticity accompanies focal hand dystonia (45–4845–4845–4845–48). Important for our hypothesis, exaggerated plasticity of the trigeminal blink reflex accompanies BEB (49). Our initial rodent model of BEB (50) used a small reduction of substantia nigra dopamine neurons to create the predisposing condition and crushing 1 branch of the facial nerve innervating the orbicularis oculi to generate the environmental trigger. The choice of dopamine depletion as a predisposing condition came from observations showing that baboons undergoing poisoning with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) of dopamine neurons exhibited dystonia before developing Parkinsonian movement abnormalities (51) and that there was a disruption of D2 receptors in patients with BEB (52,5352,53). Thus, changes in dopamine levels or the functioning of specific dopamine receptor subtypes could create the "predisposing condition" for BEB. For an environmental trigger, we created a transient eye irritation by crushing a branch of the facial nerve that provides approximately 30% of the orbicularis oculi innervation. This procedure produced a transient dry eye condition because the weakened eyelid became less effective at restoring the tear film with each blink. The condition was only temporary, however, because regeneration of the crushed nerve branch restored complete lid function within 3 weeks. In the Schicatano model (50), the BEB-like spasms of lid closure only occurred with the combination of the environmental trigger and the dopaminergic predisposing condition. In the absence of the predisposing condition, the environmental trigger of transient eye irritation slightly increased trigeminal reflex blink excitability and resulted in the development of additional blinks similar to those seen in human dry eye (20,2120,21). Without the environmental trigger, the predisposing condition of a small dopamine neuron loss slightly increased trigeminal reflex blink excitability but did not generate spasms of lid closure. Combining the predisposing condition and the environmental trigger, however, caused long-lasting spasms of lid closure, dramatically elevated trigeminal reflex blink excitability, and increased spontaneous blinking similar to the pattern of blink abnormalities of patients with BEB. These BEB-like characteristics continued after the facial nerve regained full function and eliminated the dry eye. Thus, the BEB-like characteristics of this animal model seemed to result from an exaggeration of the normally compensatory process evoked by eye irritation. The Schicatano BEB model also was consistent with the important interactions between the cerebellum and basal ganglia that underlie dystonia (54–6354–6354–6354–6354–6354–6354–6354–6354–6354–63). Previous studies demonstrated that the cerebellum was essential for adaptive responses to the eye irritation created by eyelid restraint. Lesions of the cerebellum (30,3130,31) blocked the increases in blink amplitude and duration initiated by eye irritation (20,32–3720,32–3720,32–3720,32–3720,32–3720,32–3720,32–37). Recordings from blink-related neurons in the cerebellar interpositus nucleus revealed the changes in cerebellar activity that accounted for the changes in blink amplitude and duration associated with lid restraint (29). Although the Schicatano model supported the 2 hit hypothesis as the basis of BEB and identified the basal ganglia and cerebellum as key players in this focal dystonia, the model did not explain how the predisposing condition created the exaggerated plasticity that allowed normally adaptive modification to eye irritation to swell into spasms of lid closure. We hypothesize that the key to the exaggerated plasticity of dystonia is hypersynchronized low-frequency oscillations of basal ganglia activity. Basal ganglia neurons in patients with Parkinson disease and animal models of Parkinson disease exhibit hypersynchronized oscillations in the broad beta band, 10–30 Hz (64–7164–7164–7164–7164–7164–7164–7164–71). In contrast, basal ganglia neurons in dystonic patients exhibit hypersynchronized oscillations in the theta band, 3–10 Hz (71–7471–7471–7471–74). Although the role of these oscillations in modifying voluntary movement is unclear (66,73,75–8166,73,75–8166,73,75–8166,73,75–8166,73,75–8166,73,75–8166,73,75–8166,73,75–8166,73,75–81), our study in rodents demonstrate that these basal ganglia oscillations modify trigeminal reflex blink plasticity (82). We directly tested the role of basal ganglia oscillations in blink plasticity by delivering deep brain stimulation to the basal ganglia subthalamic nucleus of normal rats undergoing a blink plasticity paradigm (82). The procedure was a cerebellar-dependent plasticity paradigm that we developed for humans (83) and modified for rodents (84). Other investigators used this paradigm to demonstrate impaired blink plasticity with Parkinson disease (85), but exaggerated blink plasticity with BEB (49). If the frequency of basal ganglia oscillations modulates brainstem plasticity, then beta frequency deep brain stimulation in normal rats should impair trigeminal reflex blink plasticity, whereas theta frequency deep brain stimulation should exaggerate blink plasticity. The Kaminer et al study (82) demonstrated the validity of this postulation. Beta frequency, 16 Hz, deep brain stimulation impaired blink plasticity, whereas theta frequency, 7 Hz, deep brain stimulation exaggerated trigeminal reflex blink plasticity in normal rats. Deep brain stimulation at 130 Hz, a therapeutic frequency for deep brain stimulation in humans (86), however, did not affect blink plasticity in normal rats. Thus, hypersynchronized theta frequency basal ganglia oscillations could create a predisposing condition in which adaptive plasticity initiated by eye irritation exaggerated into spasms of lid closure typical of BEB. In a preliminary study on 1 rat, we monitored blinking and spasms of lid closure in a normal rat receiving 7 Hz deep brain stimulation of the subthalamic nucleus 4 hours a day combined with mild dry eye produced by exorbital lacrimal gland removal (36). We tested 3 conditions: 1) 7 Hz subthalamic nucleus deep brain stimulation alone (Fig. 1B, gray bars); 2) 7 Hz subthalamic nucleus deep brain stimulation combined with dry eye (Fig. 1B, black bars); and 3) dry eye alone (Fig. 1B, white bars). In Condition 1, the rat received 5 days of 7 Hz subthalamic nucleus deep brain stimulation alone. In Condition 2, combining the predisposing condition and the environmental trigger, we removed the exorbital gland and the rat received 5 days of 7 Hz subthalamic nucleus deep brain stimulation for 4 hours each day. In Condition 3, we discontinued the 7 Hz subthalamic nucleus deep brain stimulation. For all conditions, we monitored blinking (lid closures <100 milliseconds) and lid spasms (lid closures >100 milliseconds) continuously over a 30-minute period on the last 2 days of each condition and normalized all data to the 7 Hz subthalamic nucleus deep brain stimulation alone condition. In the combined 7 Hz subthalamic nucleus deep brain stimulation and dry eye condition, the rat made more blinks than either the 7 Hz subthalamic nucleus deep brain stimulation alone or dry eye alone conditions (Fig. 1B, # Blinks). In the combined 7 Hz subthalamic nucleus deep brain stimulation and dry eye condition, the rat also exhibited more spasms of lid closure than in the other conditions (Fig. 1B, # Spasms). Moreover, the spasm duration was longer in the combined 7 Hz subthalamic nucleus deep brain stimulation and dry eye condition than in the 7 Hz subthalamic nucleus deep brain stimulation alone or dry eye alone condition (Fig. 1A, B, Spasm Dur). Finally, the rat made significantly larger blinks in the combined 7 Hz subthalamic nucleus deep brain stimulation and dry eye condition than in 7 Hz subthalamic nucleus deep brain stimulation alone condition (P < 0.05; Fig. 1B, Blink Amp). Although preliminary, these data indicate that the next rodent model of BEB should be developed by combining theta frequency deep brain stimulation of the subthalamic nucleus and dry eye.FIG. 1: An animal model of benign essential blepharospasm using 7 Hz deep brain stimulation (DBS) as the predisposing condition. A. A recording of spasms of lid closure and excessive blinking by a rat with dry eye receiving 7 Hz subthalamic nucleus (STN) DBS. B. Average number of blinks (# Blinks), blink amplitude (Blink amp), blink duration (Blink Dur), number of spasms (# Spasms), amplitude of spasms (Spasm Amp), and duration of spasms (Spasm Dur) relative to 7 Hz STN DBS alone condition. Spasms were lid closures lasting >100 milliseconds. Error bars are SEM. *P < 0.05; ***P < 0.001.Thus far, animal models of BEB have not been tested for the abnormal sensitivity to light associated with BEB (1,24,871,24,871,24,87). The neural bases of photophobia in patients with BEB are unknown. Physiological and behavioral studies of photophobia implicate changes in blood flow (88), melanopsin ganglion cell inputs to somatosensory thalamic regions (89), intraocular nociceptors (90), and calcitonin gene-related peptide trigeminal sensitization (91,9291,92). Because all of these mechanisms involve elevated trigeminal excitability, we anticipate that rodent models of BEB will also exhibit exaggerated light sensitivity. The evidence from animal models indicates that spasms of lid closure and trigeminal hyperexcitability of BEB result from exaggerated neuroplasticity, an amplification of the normally adaptive modifications of blinking initiated by eye irritation. The adaptive plasticity initiated by eye irritation seems to involve the cerebellum (29–3129–3129–31), and the exaggeration of plasticity ensues from abnormal basal ganglia modulation of cerebellar activity (82). These results are consistent with the available data pointing to abnormal cerebellar basal ganglia interactions as a major component of dystonia (62,93–9662,93–9662,93–9662,93–9662,93–96). Although animal models are not identical to human BEB, they are invaluable for identifying the neural mechanisms and circuits causing BEB.

The synchronized beta‐band oscillations in the basal ganglia‐cortical networks in Parkinson's disease (PD) may be responsible for PD motor symptoms or an epiphenomenon of dopamine loss. We investigated the causal role of beta‐band activity in PD motor symptoms by testing the effects of beta‐frequency subthalamic nucleus deep‐brain stimulation (STN DBS) on the blink reflex excitability, amplitude, and plasticity in normal rats. Delivering 16 Hz STN DBS produced the same increase in blink reflex excitability and impairment in blink reflex plasticity in normal rats as occurs in rats with 6‐hydroxydopamine lesions and patients with PD. These deficits were not an artifact of STN DBS because, when these normal rats received 130 Hz STN DBS, their blink characteristics were the same as without STN DBS. To demonstrate that the blink reflex disturbances with 16 Hz STN DBS were frequency specific, we tested the same rats with 7 Hz STN DBS, a theta‐band frequency typical of dystonia. In contrast to beta stimulation, 7 Hz STN DBS exaggerated the blink reflex plasticity as occurs in focal dystonia. Thus, without destroying dopamine neurons or blocking dopamine receptors, frequency‐specific STN DBS can be used to create PD‐like or dystonic‐like symptoms in a normal rat.

37 Reflex blinks provide a model system for investigating motor learning in normal and 38 pathological states. We investigated whether high frequency stimulation of the supraor39 bital branch of the trigeminal nerve before the R2 blink component (HFS-B) decreases 40 reflex blink gain in alert rats. As with humans (Mao and Evinger 2001), HFS-B signifi41 cantly reduced blink size in the first hour after treatment for rats. Repeated days of HFS42 B treatment produced long-term depression of blink circuits. Blink gain decreased expo43 nentially across days indicating a long-term depression of blink circuits. Additionally, 44 the HFS-B protocol became more effective at depressing blink amplitude across days of 45 treatment. This depression was not habituation because neither longnor short-term 46 blink changes occurred when presenting HFS after the R2. To investigate whether gain 47 modifications produced by HFS-B involved cerebellar networks, we trained rats in a de48 lay eyelid conditioning paradigm using HFS-B as the unconditioned stimulus and a tone 49 as the conditioned stimulus. As HFS-B depresses blink circuits and delay conditioning 50 enhances blink circuit activity, occlusion should occur if they share neural networks. 51 Rats acquiring robust eyelid conditioning did not exhibit decreases in blink gain, whereas 52 rats developing low levels of eyelid conditioning exhibited weak, short-term reductions in 53 blink gain. These results suggested that delay eyelid conditioning and long-term HFS-B 54 utilize some of the same cerebellar circuits. The ability of repeated HFS-B treatment to 55 depress trigeminal blink circuit activity long-term implied that it may be a useful protocol 56 to reduce hyperexcitable blink circuits that underlie diseases like benign essential 57

The focal dystonia benign essential blepharospasm (BEB) affects as many as 40,000 individuals in the United States. This dystonia is characterized by trigeminal hyperexcitability, photophobia, and most disabling of the symptoms, involuntary spasms of lid closure that can produce functional blindness. Like many focal dystonias, BEB appears to develop from the interaction between a predisposing condition and an environmental trigger. The primary treatment for blepharospasm is to weaken the eyelid-closing orbicularis oculi muscle to reduce lid spasms. There are several animal models of blepharospasm that recreate the spasms of lid closure in order to investigate pharmacological treatments to prevent spasms of lid closure. One animal model attempts to mimic the predisposing condition and environmental trigger that give rise to BEB. This model indicates that abnormal interactions among trigeminal blink circuits, basal ganglia, and the cerebellum are the neural basis for BEB.

Reflex blinks provide a model system for investigating motor learning in normal and pathological states. We investigated whether high-frequency stimulation (HFS) of the supraorbital branch of the trigeminal nerve before the R2 blink component (HFS-B) decreases reflex blink gain in alert rats. As with humans (Mao JB, Evinger C. J Neurosci 21: RC151, 2001), HFS-B significantly reduced blink size in the first hour after treatment for rats. Repeated days of HFS-B treatment produced long-term depression of blink circuits. Blink gain decreased exponentially across days, indicating a long-term depression of blink circuits. Additionally, the HFS-B protocol became more effective at depressing blink amplitude across days of treatment. This depression was not habituation, because neither long- nor short-term blink changes occurred when HFS was presented after the R2. To investigate whether gain modifications produced by HFS-B involved cerebellar networks, we trained rats in a delay eyelid conditioning paradigm using HFS-B as the unconditioned stimulus and a tone as the conditioned stimulus. As HFS-B depresses blink circuits and delay conditioning enhances blink circuit activity, occlusion should occur if they share neural networks. Rats acquiring robust eyelid conditioning did not exhibit decreases in blink gain, whereas rats developing low levels of eyelid conditioning exhibited weak, short-term reductions in blink gain. These results suggested that delay eyelid conditioning and long-term HFS-B utilize some of the same cerebellar circuits. The ability of repeated HFS-B treatment to depress trigeminal blink circuit activity long term implied that it may be a useful protocol to reduce hyperexcitable blink circuits that underlie diseases like benign essential blepharospasm.

Memory-guided saccades are slower than visually guided saccades. The usual explanation for this slowing is that the absence of a visual drive reduces the discharge of neurons in the superior colliculus. We tested a related hypothesis: that the slowing of memory-guided saccades was due also to the more frequent occurrence of gaze-evoked blinks with memory-guided saccades compared with visually guided saccades. We recorded gaze-evoked blinks in three monkeys while they performed visually guided and memory-guided saccades and compared the kinematics of the different saccade types with and without blinks. Gaze-evoked blinks were more common during memory-guided saccades than during visually guided saccades, and the well-established relationship between peak and average velocity for saccades was disrupted by blinking. The occurrence of gaze-evoked blinks was associated with a greater slowing of memory-guided saccades compared with visually guided saccades. Likewise, when blinks were absent, the peak velocity of visually guided saccades was only slightly higher than that of memory-guided saccades. Our results reveal interactions between circuits generating saccades and blink-evoked eye movements. The interaction leads to increased curvature of saccade trajectories and a corresponding decrease in saccade velocity. Consistent with this interpretation, the amount of saccade curvature and slowing increased with gaze-evoked blink amplitude. Thus, although the absence of vision decreases the velocity of memory-guided saccades relative to visually guided saccades somewhat, the cooccurrence of gaze-evoked blinks produces the majority of slowing for memory-guided saccades.

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.

PURPOSEThe authors investigated whether trigeminal sensitization occurs in response to bright light with the retina disconnected from the rest of the central nervous system by optic nerve section.METHODSIn urethane-anesthetized rats, trigeminal reflex blinks were evoked with air puff stimuli directed at the cornea in darkness and at three different light intensities. After normative data were collected, the optic nerve was lesioned and the rats were retested. In an alert rat, reflex blinks were evoked by stimulation of the supraorbital branch of the trigeminal nerve in the dark and in the light.RESULTSA 9.1 × 10(3) μW/cm(2) and a 15.1 × 10(3) μW/cm(2) light significantly enhanced the magnitude of reflex blinks relative to blinks evoked by the same trigeminal stimulus when the rats were in the dark. In addition, rats exhibited a significant increase in spontaneous blinking in the light relative to the blink rate in darkness. After lesioning of the optic nerve, the 15.1 × 10(3) μW/cm(2) light still significantly increased the magnitude of trigeminal reflex blinks.CONCLUSIONSBright lights increase trigeminal reflex blink amplitude and the rate of spontaneous blinking in rodents. Light can modify trigeminal activity without involving the central visual system.

Blinking of the eyelids protects the eye and ensures corneal hydration. The eyelids must also move coordinately with eye rotation to maintain vision during upward eye movements. The neural control of eyelids is interconnected with brainstem circuits producing saccadic eye movements. The nervous system exhibits adaptive modifications that enable the eyelids to compensate for cornea irritation and dry eye. These modifications involve the trigeminal complex and the cerebellum. Blepharospasm and hemifacial spasm are focal dystonias with disruption of eye blink control mechanisms. Current studies indicate that both these disorders are caused by predisposition of the individual combined with precipitating factors.

Based on kinematic properties and distinct substrates, there are different classes of eyelid movement described as eyeblinks. We investigate whether the eyelid movements made in response to a conditioned stimulus (CS) are a category of eyelid movements distinct from blinks. Human subjects received 60 trials of classical eyelid conditioning with a tone as the CS and electrical stimulation of the supraorbital branch of the trigeminal nerve as the unconditioned stimulus (UCS). Before and after training, reflex blinks were elicited with the UCS. The kinematics of conditioned responses (CRs) differed significantly from those of reflex blinks. The slope of the amplitude-maximum velocity function was steeper for reflex blinks than for CRs, and reflex blink duration was significantly shorter than CR duration. Unlike reflex blinks, for which maximum velocity was independent of blink duration, the maximum velocity of CRs depended on CR duration. These quantitative and qualitative differences indicated that CRs were a unique class of eyelid movements distinct from blinks and eyelid movements with vertical saccadic gaze shifts.

To analyze properly the role of the cerebellum in classical conditioning of the eyeblink and nictitating membrane (NM) response, the control of conditioned response dynamics must be better understood. Previous studies have suggested that the control signal is linearly related to the CR as a result of recruitment within the accessory abducens motoneuron pool, which acts to linearize retractor bulbi muscle and NM response mechanics. Here we investigate possible recruitment mechanisms. Data came from simultaneous recordings of NM position and multiunit electromyographic (EMG) activity from the retractor bulbi muscle of rabbits during eyeblink conditioning, in which tone and periocular shock act as conditional and unconditional stimuli, respectively. Action potentials (spikes) were extracted and classified by amplitude. Firing rates of spikes with different amplitudes were analyzed with respect to NM response temporal profiles and total EMG spike firing rate. Four main regularities were revealed and quantified: 1) spike amplitude increased with response amplitude; 2) smaller spikes always appeared before larger spikes; 3) subsequent firing rates covaried for spikes of different amplitude, with smaller spikes always firing at higher rates than larger ones; and 4) firing-rate profiles were approximately Gaussian for all amplitudes. These regularities suggest that recruitment does take place in the retractor bulbi muscle during conditioned NM responses and that all motoneurons receive the same command signal (common-drive hypothesis). To test this hypothesis, a model of the motoneuron pool was constructed in which motoneurons had a range of intrinsic thresholds distributed exponentially, with threshold linearly related to EMG spike amplitude. Each neuron received the same input signal as required by the common-drive assumption. This simple model reproduced the main features of the data, suggesting that conditioned NM responses are controlled by a common-drive mechanism that enables simple commands to determine response topography in a linear fashion.