The ultrastructure of macaque mesencephalic trigeminal nucleus neurons.

Primary afferents originating from the mesencephalic trigeminal nucleus provide the main source of proprioceptive information guiding mastication, and thus represent an important component of this critical function. Unlike those of other primary afferents, their cell bodies lie within the central nervous system. It is believed that this unusual central location allows them to be regulated by synaptic input. In this study, we explored the ultrastructure of macaque mesencephalic trigeminal nucleus neurons to determine the presence and nature of this synaptic input in a primate. We first confirmed the location of macaque mesencephalic trigeminal neurons by retrograde labeling from the masticatory muscles. Since the labeled neurons were by far the largest cells located at the edge of the periaqueductal gray, we could undertake sampling for electron microscopy based on soma size. Ultrastructurally, mesencephalic trigeminal neurons had very large somata with euchromatic nuclei that sometimes displayed deeply indented nuclear membranes. Terminal profiles with varied vesicle characteristics and synaptic density thicknesses were found in contact with either their somatic plasma membranes or somatic spines. However, in contradistinction to other, much smaller, somata in the region, the plasma membranes of the mesencephalic trigeminal somata had only a few synaptic contacts. They did extend numerous somatic spines of various lengths into the neuropil, but most of these also lacked synaptic contact. The observed ultrastructural organization indicates that macaque trigeminal mesencephalic neurons do receive synaptic contacts, but despite their central location, they only avail themselves of very limited input.

Brainstem sources of input to the central mesencephalic reticular formation in the macaque.

Physiological studies indicate that the central mesencephalic reticular formation (cMRF) plays a role in gaze changes, including control of disjunctive saccades. Neuroanatomical studies have demonstrated strong interconnections with the superior colliculus, along with projections to extraocular motor nuclei, the preganglionic nucleus of Edinger-Westphal, the paramedian pontine reticular formation, nucleus raphe interpositus, medullary reticular formation and cervical spinal cord, as might be expected for a structure that is intimately involved in gaze control. However, the sources of input to this midbrain structure have not been described in detail. In the present study, the brainstem cells of origin supplying the cMRF were labeled by retrograde transport of tracer (wheat germ agglutinin conjugated horseradish peroxidase) in macaque monkeys. Within the diencephalon, labeled neurons were noted in the ventromedial nucleus of the hypothalamus, pregeniculate nucleus and habenula. In the midbrain, labeled cells were found in the substantia nigra pars reticulata, medial pretectal nucleus, superior colliculus, tectal longitudinal column, periaqueductal gray, supraoculomotor area, and contralateral cMRF. In the pons they were located in the paralemniscal zone, parabrachial nucleus, locus coeruleus, nucleus prepositus hypoglossi and the paramedian pontine reticular formation. Finally, in the medulla they were observed in the medullary reticular formation. The fact that this list of input sources is very similar to those of the superior colliculus supports the view that the cMRF represents an important gaze control center.

Neural control of rapid binocular eye movements: Saccade-vergence burst neurons.

During normal viewing, we direct our eyes between objects in three-dimensional (3D) space many times a minute. To accurately fixate these objects, which are usually located in different directions and at different distances, we must generate eye movements with appropriate versional and vergence components. These combined saccade-vergence eye movements result in disjunctive saccades with a vergence component that is much faster than that generated during smooth, symmetric vergence eye movements. The neural control of disjunctive saccades is still poorly understood. Recent anatomical studies suggested that the central mesencephalic reticular formation (cMRF), located lateral to the oculomotor nucleus, contains premotor neurons potentially involved in the neural control of these eye movements. We have therefore investigated the role of the cMRF in the control of disjunctive saccades in trained rhesus monkeys. Here, we describe a unique population of cMRF neurons that, during disjunctive saccades, display a burst of spikes that are highly correlated with vergence velocity. Importantly, these neurons show no increase in activity for either conjugate saccades or symmetric vergence. These neurons are termed saccade-vergence burst neurons (SVBNs) to maintain consistency with modeling studies that proposed that such a class of neuron exists to generate the enhanced vergence velocities observed during disjunctive saccades. Our results demonstrate the existence and characteristics of SVBNs whose activity is correlated solely with the vergence component of disjunctive saccades and, based on modeling studies, are critically involved in the generation of the disjunctive saccades required to view objects in our 3D world.

Superior colliculus projections to target populations in the supraoculomotor area of the macaque monkey.

A projection by the superior colliculus to the supraoculomotor area (SOA) located dorsal to the oculomotor complex was first described in 1978. This projection's targets have yet to be identified, although the initial study suggested that vertical gaze motoneuron dendrites might receive this input. Defining the tectal targets is complicated by the fact the SOA contains a number of different cell populations. In the present study, we used anterograde tracers to characterize collicular axonal arbors and retrograde tracers to label prospective SOA target populations in macaque monkeys. Close associations were not found with either superior or medial rectus motoneurons whose axons supply singly innervated muscle fibers. S-group motoneurons, which supply superior rectus multiply innervated muscle fibers, appeared to receive a very minor input, but C-group motoneurons, which supply medial rectus multiply innervated muscle fibers, received no input. A number of labeled boutons were observed in close association with SOA neurons projecting to the spinal cord, or the reticular formation in the pons and medulla. These descending output neurons are presumed to be peptidergic cells within the centrally projecting Edinger-Westphal population. It is possible the collicular input provides a signaling function for neurons in this population that serve roles in either stress responses, or in eating and drinking behavior. Finally, a number of close associations were observed between tectal terminals and levator palpebrae superioris motoneurons, suggesting the possibility that the superior colliculus provides a modest direct input for raising the eyelids during upward saccades.

Cerebellar projections to the macaque midbrain tegmentum: Possible near response connections.

Since most gaze shifts are to targets that lie at a different distance from the viewer than the current target, gaze changes commonly require a change in the angle between the eyes. As part of this response, lens curvature must also be adjusted with respect to target distance by the ciliary muscle. It has been suggested that projections by the cerebellar fastigial and posterior interposed nuclei to the supraoculomotor area (SOA), which lies immediately dorsal to the oculomotor nucleus and contains near response neurons, support this behavior. However, the SOA also contains motoneurons that supply multiply innervated muscle fibers (MIFs) and the dendrites of levator palpebrae superioris motoneurons. To better determine the targets of the fastigial nucleus in the SOA, we placed an anterograde tracer into this cerebellar nucleus in Macaca fascicularis monkeys and a retrograde tracer into their contralateral medial rectus, superior rectus, and levator palpebrae muscles. We only observed close associations between anterogradely labeled boutons and the dendrites of medial rectus MIF and levator palpebrae motoneurons. However, relatively few of these associations were present, suggesting these are not the main cerebellar targets. In contrast, labeled boutons in SOA, and in the adjacent central mesencephalic reticular formation (cMRF), densely innervated a subpopulation of neurons. Based on their location, these cells may represent premotor near response neurons that supply medial rectus and preganglionic Edinger-Westphal motoneurons. We also identified lens accommodation-related cerebellar afferent neurons via retrograde trans-synaptic transport of the N2c rabies virus from the ciliary muscle. They were found bilaterally in the fastigial and posterior interposed nuclei, in a distribution which mirrored that of neurons retrogradely labeled from the SOA and cMRF. Our results suggest these cerebellar neurons coordinate elements of the near response during symmetric vergence and disjunctive saccades by targeting cMRF and SOA premotor neurons.

Central mesencephalic reticular formation control of the near response: lens accommodation circuits.

To view a nearby target, the three components of the near response are brought into play: 1) the eyes are converged through contraction of the medial rectus muscles to direct both foveae at the target, 2) the ciliary muscle contracts to allow the lens to thicken, increasing its refractive power to focus the near target on the retina, and 3) the pupil constricts to increase depth of field. In this study, we utilized retrograde transsynaptic transport of the N2c strain of rabies virus injected into the ciliary body of one eye of macaque monkeys to identify premotor neurons that control lens accommodation. We previously used this approach to label a premotor population located in the supraoculomotor area. In the present report, we describe a set of neurons located bilaterally in the central mesencephalic reticular formation that are labeled in the same time frame as the supraoculomotor area population, indicating their premotor character. The labeled premotor neurons are mostly multipolar cells, with long, very sparsely branched dendrites. They form a band that stretches across the core of the midbrain reticular formation. This population appears to be continuous with the premotor near-response neurons located in the supraoculomotor area at the level of the caudal central subdivision of the oculomotor nucleus. The central mesencephalic reticular formation has previously been associated with horizontal saccadic eye movements, so these premotor cells might be involved in controlling lens accommodation during disjunctive saccades. Alternatively, they may represent a population that controls vergence velocity. NEW & NOTEWORTHY This report uses transsynaptic transport of rabies virus to provide new evidence that the central mesencephalic reticular formation (cMRF) contains premotor neurons controlling lens accommodation. When combined with other recent reports that the cMRF also contains premotor neurons supplying medial rectus motoneurons, these results indicate that this portion of the reticular formation plays an important role in directing the near response and disjunctive saccades when viewers look between targets located at different distances.

Task dependence of decision- and choice-related activity in monkey oculomotor thalamus.

Oculomotor signals circulate within putative recurrent feedback loops that include the frontal eye field (FEF) and the oculomotor thalamus (OcTh). To examine how OcTh contributes to visuomotor control, and perceptually informed saccadic choices in particular, neural correlates of perceptual judgment and motor selection in OcTh were evaluated and compared with those previously reported for FEF in the same subjects. Monkeys performed three tasks: a choice task in which perceptual decisions are urgent, a choice task in which identical decisions are made without time pressure, and a single-target, delayed saccade task. The OcTh yielded far fewer task-responsive neurons than the FEF, but across responsive pools, similar neuron types were found, ranging from purely visual to purely saccade related. Across such types, the impact of the perceptual information relevant to saccadic choices was qualitatively the same in FEF and OcTh. However, distinct from that in FEF, activity in OcTh was strongly task dependent, typically being most vigorous in the urgent task, less so in the easier choice task, and least in the single-target task. This was true for responsive and nonresponsive cells alike. Neurons with exclusively motor-related activity showed strong task dependence, fired less, and differed most patently from their FEF counterparts, whereas those that combined visual and motor activity fired most similarly to their FEF counterparts. The results suggest that OcTh activity is more distantly related to saccade production per se, because its degree of commitment to a motor choice varies markedly as a function of ongoing cognitive or behavioral demands.

Mechanics of mouse ocular motor plant quantified by optogenetic techniques.

Rigorous descriptions of ocular motor mechanics are often needed for models of ocular motor circuits. The mouse has become an important tool for ocular motor studies, yet most mechanical data come from larger species. Recordings of mouse abducens neurons indicate the mouse mechanics share basic viscoelastic properties with larger species but have considerably longer time constants. Time constants can also be extracted from the rate at which the eye re-centers when released from an eccentric position. The displacement can be accomplished by electrically stimulating ocular motor nuclei, but electrical stimulation may also activate nearby ocular motor circuitry. We achieved specific activation of abducens motoneurons through photostimulation in transgenic mice expressing channelrhodopsin in cholinergic neurons. Histology confirmed strong channelrhodopsin expression in the abducens nucleus with relatively little expression in nearby ocular motor structures. Stimulation was delivered as 20- to 1,000-ms pulses and 40-Hz trains. Relaxations were modeled best by a two-element viscoelastic system. Time constants were sensitive to stimulus duration. Analysis of isometric relaxation of isolated mouse extraocular muscles suggest the dependence is attributable to noninstantaneous decay of active forces in non-twitch fibers following stimulus offset. Time constants were several times longer than those obtained in primates, confirming that the mouse ocular motor mechanics are relatively sluggish. Finally, we explored the effects of 0.1- to 20-Hz sinusoidal photostimuli and demonstrated their potential usefulness in characterizing ocular motor mechanics, although this application will require further data on the temporal relationship between photostimulation and neuronal firing in extraocular motoneurons.

Anatomical evidence that the superior colliculus controls saccades through central mesencephalic reticular formation gating of omnipause neuron activity.

Omnipause neurons (OPNs) within the nucleus raphe interpositus (RIP) help gate the transition between fixation and saccadic eye movements by monosynaptically suppressing activity in premotor burst neurons during fixation, and releasing them during saccades. Premotor neuron activity is initiated by excitatory input from the superior colliculus (SC), but how the tectum's saccade-related activity turns off OPNs is not known. Since the central mesencephalic reticular formation (cMRF) is a major SC target, we explored whether this nucleus has the appropriate connections to support tectal gating of OPN activity. In dual-tracer experiments undertaken in macaque monkeys (Macaca fascicularis), cMRF neurons labeled retrogradely from injections into RIP had numerous anterogradely labeled terminals closely associated with them following SC injections. This suggested the presence of an SC-cMRF-RIP pathway. Furthermore, anterograde tracers injected into the cMRF of other macaques labeled axonal terminals in RIP, confirming this cMRF projection. To determine whether the cMRF projections gate OPN activity, postembedding electron microscopic immunochemistry was performed on anterogradely labeled cMRF terminals with antibody to GABA or glycine. Of the terminals analyzed, 51.4% were GABA positive, 35.5% were GABA negative, and most contacted glycinergic cells. In summary, a trans-cMRF pathway connecting the SC to the RIP is present. This pathway contains inhibitory elements that could help gate omnipause activity and allow other tectal drives to induce the bursts of firing in premotor neurons that are necessary for saccades. The non-GABAergic cMRF terminals may derive from fixation units in the cMRF.

Axons giving rise to the palisade endings of feline extraocular muscles display motor features.

Palisade endings are nerve specializations found in the extraocular muscles (EOMs) of mammals, including primates. They have long been postulated to be proprioceptors. It was recently demonstrated that palisade endings are cholinergic and that in monkeys they originate from the EOM motor nuclei. Nevertheless, there is considerable difference of opinion concerning the nature of palisade ending function. Palisade endings in EOMs were examined in cats to test whether they display motor or sensory characteristics. We injected an anterograde tracer into the oculomotor or abducens nuclei and combined tracer visualization with immunohistochemistry and α-bungarotoxin staining. Employing immunohistochemistry, we performed molecular analyses of palisade endings and trigeminal ganglia to determine whether cat palisade endings are a cholinergic trigeminal projection. We confirmed that palisade endings are cholinergic and showed, for the first time, that they, like extraocular motoneurons, are also immunoreactive for calcitonin gene-related peptide. Following tracer injection into the EOM nuclei, we observed tracer-positive palisade endings that exhibited choline acetyl transferase immunoreactivity. The tracer-positive nerve fibers supplying palisade endings also established motor terminals along the muscle fibers, as demonstrated by α-bungarotoxin. Neither the trigeminal ganglion nor the ophthalmic branch of the trigeminal nerve contained cholinergic elements. This study confirms that palisade endings originate in the EOM motor nuclei and further indicates that they are extensions of the axons supplying the muscle fiber related to the palisade. The present work excludes the possibility that they receive cholinergic trigeminal projections. These findings call into doubt the proposed proprioceptive function of palisade endings.

Expression of mineralocorticoid and glucocorticoid receptors in preautonomic neurons of the rat paraventricular nucleus.

Activation of mineralocorticoid receptors (MR) of the hypothalamic paraventricular nucleus (PVN) increases sympathetic excitation. To determine whether MR and glucocorticoid receptors (GR) are expressed in preautonomic neurons of the PVN and how they relate to endogenous aldosterone levels in healthy rats, retrograde tracer was injected into the intermediolateral cell column at T4 to identify preautonomic neurons in the PVN. Expression of MR, GR, 11-ß hydroxysteroid dehydrogenase1 and 2 (11ß-HSD1, 2), and hexose-6-phosphate dehydrogenase (H6PD) required for 11ß-HSD1 reductase activity was assessed by immunohistochemistry. RT-PCR and Western blot analysis were used to determine MR gene and protein expression. Most preautonomic neurons were in the caudal mediocellular region of PVN, and most expressed MR; none expressed GR. 11ß-HSD1, but not 11ß-HSD2 nor H6PD immunoreactivity, was detected in the PVN. In rats with chronic low or high sodium intakes, the low-sodium diet was associated with significantly higher plasma aldosterone, MR mRNA and protein expression, and c-Fos immunoreactivity within labeled preautonomic neurons. Plasma corticosterone and sodium and expression of tonicity-responsive enhancer binding protein in the PVN did not differ between groups, suggesting osmotic adaptation to the altered sodium intake. These results suggest that MR within preautonomic neurons in the PVN directly participate in the regulation of sympathetic nervous system drive, and aldosterone may be a relevant ligand for MR in preautonomic neurons of the PVN under physiological conditions. Dehydrogenase activity of 11ß-HSD1 occurs in the absence of H6PD, which regenerates NADP(+) from NADPH and may increase MR gene expression under physiological conditions.

The superior colliculus projection upon the macaque inferior olive.

Saccade accommodation is a productive model for exploring the role of the cerebellum in behavioral plasticity. In this model, the target is moved during the saccade, gradually inducing a change in the saccade vector as the animal adapts. The climbing fiber pathway from the inferior olive provides a visual error signal generated by the superior colliculus that is believed to be crucial for cerebellar adaptation. However, the primate tecto-olivary pathway has only been explored using large injections of the central portion of the superior colliculus. To provide a more detailed picture, we have made injections of anterograde tracers into various regions of the macaque superior colliculus. As shown previously, large central injections primarily label a dense terminal field within the C subdivision at caudal end of the contralateral medial inferior olive. Several, previously unobserved, sites of sparse terminal labeling were noted: bilaterally in the dorsal cap of Kooy and ipsilaterally in the C subdivision of the medial inferior olive. Small, physiologically directed, injections into the rostral, small saccade portion of the superior colliculus produced terminal fields in the same regions of the medial inferior olive, but with decreased density. Small injections of the caudal superior colliculus, where large amplitude gaze changes are encoded, again labeled a terminal field located in the same areas. The lack of a topographic pattern within the main tecto-olivary projection suggests that either the precise vector of the visual error is not transmitted to the vermis, or that encoding of this error is via non-topographic means.

Mesencephalic trigeminal neuron dendritic structures in the macaque.

It is presumed that the unusual central location of mesencephalic trigeminal neurons is a specialization that allows them to receive synaptic input. However, relatively few synaptic terminals were observed on the somata of mesencephalic trigeminal neurons in macaque monkeys via electron microscopy. This leaves the question of dendritic synaptic terminals open. Unlike the pseudounipolar neurons found in the trigeminal ganglion, some mesencephalic trigeminal neurons have been reported to be multipolar cells exhibiting a number of dendritic processes in non-primate species. To examine whether this morphological feature was also present in macaque monkeys, we retrogradely filled these cells with biotinylated dextran amine by injecting it into the trigeminal nerve entry zone. A portion of the mesencephalic trigeminal neurons exhibited short, poorly branched, dendritic processes. They also exhibited very fine, short processes believed to be somatic spines. Thus, primate trigeminal mesencephalic neurons appear to have specializations aimed at increasing the membrane surface area available for synaptic input.

Activity of the Substantia Nigra Pars Reticulata during Saccade Adaptation.

When movements become inaccurate, the resultant error induces motor adaptation to improve accuracy. This error-based motor learning is regarded as a cerebellar function. However, the influence of the other brain areas on adaptation is poorly understood. During saccade adaptation, a type of error-based motor learning, the superior colliculus (SC) sends a postsaccadic error signal to the cerebellum to drive adaptation. Since the SC is directly inhibited by the substantia nigra pars reticulata (SNr), we hypothesized that the SNr might influence saccade adaptation by affecting the SC error signal. In fact, previous studies indicated that the SNr encodes motivation and motivation influences saccade adaptation. In this study, we first established that the SNr projects to the rostral SC, where small error signals are generated, in nonhuman primates. Then, we examined SNr activity while the animal underwent adaptation. SNr neurons paused their activity in association with the error. This pause was shallower and delayed compared with those of no-error trial saccades. The pause at the end of the adaptation was shallower and delayed compared with that at the beginning of the adaptation. The change in the intertrial interval, an indicator of motivation, and adaptation speed had a positive correlation with the changes in the error-related pause. These results suggest that (1) the SNr exhibits a unique activity pattern during the error interval; (2) SNr activity increases during adaptation, consistent with the decrease in SC activity; and (3) motivational decay during the adaptation session might increase SNr activity and influence the adaptation speed.

The Superior Colliculus Projection Upon the Macaque Inferior Olive.

Saccade accommodation is a productive model for exploring the role of the cerebellum in behavioral plasticity. In this model, the target is moved during the saccade, gradually inducing a change in the saccade vector as the animal adapts. The climbing fiber pathway from the inferior olive provides a visual error signal generated by the superior colliculus that is believed to be crucial for cerebellar adaptation. However, the primate tecto-olivary pathway has only been explored using large injections of the central portion of the superior colliculus. To provide a more detailed picture, we have made injections of anterograde tracers into various regions of the macaque superior colliculus. As shown previously, large central injections primarily label a dense terminal field within the C subdivision at caudal end of the contralateral medial inferior olive. Several, previously unobserved, sites of sparse terminal labeling were noted: bilaterally in the dorsal cap of Kooy and ipsilaterally in C subdivision of the medial inferior olive. Small, physiologically directed, injections into the rostral, small saccade portion of the superior colliculus produced terminal fields in the same regions of the medial inferior olive, but with decreased density. Small injections of the caudal superior colliculus, where large amplitude gaze changes are encoded, again labeled a terminal field located in the same areas. The lack of a topographic pattern within the main tecto-olivary projection suggests that either the precise vector of the visual error is not transmitted to the vermis, or that encoding of this error is via non-topographic means.

A Novel Tectal/Pretectal Population of Premotor Lens Accommodation Neurons.

Purpose: Under real-world conditions, saccades are often accompanied by changes in vergence angle and lens accommodation that compensate for changes in the distance between the current fixation point and the next target. As the superior colliculus directs saccades, we examined whether it contains premotor neurons that might control lens compensation for target distance. Methods: Rabies virus or recombinant rabies virus was injected into the ciliary bodies of Macaca fascicularis monkeys to label circuits controlling lens accommodation via retrograde transsynaptic transport. In addition, conventional anterograde tracers were used to confirm the rabies findings with respect to projections to preganglionic Edinger-Westphal motoneurons. Results: At time courses that rabies virus labeled lens-related premotor neurons in the supraoculomotor area and central mesencephalic reticular formation, labeled neurons were not found within the superior colliculus. They were, however, found bilaterally in the medial pretectal nucleus continuing caudally into the tectal longitudinal column, which lies on the midline, between the colliculi. A bilateral projection by this area to the preganglionic Edinger-Westphal nucleus was confirmed by anterograde tracing. Only at longer time courses were cells labeled in the superior colliculus. Conclusions: The superior colliculus does not provide premotor input to preganglionic Edinger-Westphal nucleus motoneurons, but may provide input to lens-related premotor populations in the supraoculomotor area and central mesencephalic reticular formation. There is, however, a novel third population of lens-related premotor neurons in the tectal longitudinal column and rostrally adjacent medial pretectal nucleus. The specific function of this premotor population remains to be determined.

Is the central mesencephalic reticular formation a purely horizontal gaze center?

Historically, the central mesencephalic reticular formation has been regarded as a purely horizontal gaze center based on the fact that electrical stimulation of this region produces horizontal saccades, it provides monosynaptic input to medial rectus motoneurons, and cells recorded in this region often display a peak in firing when horizontal saccades are made. We tested the proposition that the central mesencephalic reticular formation is purely a horizontal gaze center by examining whether this region also supplies terminals to superior rectus and levator palpebrae superioris motoneurons, both of which fire when making vertical eye movements. The experiments were carried out using dual tracer techniques at the light and electron microscopic level in macaque monkeys. Injections of biotinylated dextran amine or Phaseolus vulgaris leukoagglutinin into the central mesencephalic reticular formation produced anterogradely labeled terminals that were in synaptic contact with superior rectus and levator palpebrae superioris motoneurons that had been retrogradely labeled. These results indicate that this region is not purely connected with horizontal gaze motoneurons. In addition, we found that the number of contacts on vertical gaze motoneurons increased with more rostral injections involving the mesencephalic reticular formation adjacent to the interstitial nucleus of Cajal. This suggests that there is a caudal to rostral gradient for horizontal to vertical saccades, respectively, represented within the midbrain reticular formation. Finally, we utilized post-embedding immunohistochemistry to show that a portion of the labeled terminals were GABAergic, indicating they likely originate from downgaze premotor neurons.

The Substantia Nigra Pars Reticulata Modulates Error-Based Saccadic Learning in Monkeys.

The basal ganglia have long been considered crucial for associative learning, but whether they also are involved in another type of learning, error-based motor learning, is not clear. Error-based learning has been considered the province of the cerebellum. However, learning to use a robotic arm and saccade adaptation, which use error-based learning, are facilitated by motivation, which is a function of the basal ganglia. Additionally, patients with Parkinson's disease, a basal ganglia deficit, show slower saccade adaptation than age matched controls. To further investigate whether the basal ganglia actually influence error-based learning, we reversibly inactivated the oculomotor portion of the substantia nigra pars reticulata (SNr) in two monkeys and tested saccade adaptation. Here, we show that nigral inactivation affected saccade adaptation. In particular, the inactivation facilitated the amplitude decrease adaptation of ipsiversive saccades. Consistent with previous studies, no effect was seen on the amplitude of the ipsiversive saccades when we did not induce adaptation. Therefore, the facilitated adaptation was not caused by inactivation directly modulating ipsiversive saccades. On the other hand, the kinematics of corrective saccades, which represent error processing, were changed after the inactivation. Thus, our data suggest that the oculomotor SNr assists saccade adaptation by strengthening the error signal. This effect indicates the basal ganglia influence error-based motor learning, a previously unrecognized function.

Macaque monkey trigeminal blink reflex circuits targeting levator palpebrae superioris motoneurons.

For normal viewing, the eyes are held open by the tonic actions of the levator palpebrae superioris (levator) muscle raising the upper eyelid. This activity is interrupted during blinks, when the eyelid sweeps down to spread the tear film or protect the cornea. We examined the circuit connecting the principal trigeminal nucleus to the levator motoneurons by use of both anterograde and retrograde tracers in macaque monkeys. Injections of anterograde tracer were made into the principal trigeminal nucleus using either a stereotaxic approach or localization following physiological characterization of trigeminal second order neurons. Anterogradely labeled axonal arbors were located both within the caudal central subdivision, which contains levator motoneurons, and in the adjacent supraoculomotor area. Labeled boutons made synaptic contacts on retrogradely labeled levator motoneurons indicating a monosynaptic connection. As the eye is also retracted through the actions of the rectus muscles during a blink, we examined whether these trigeminal injections labeled boutons contacting rectus motoneurons within the oculomotor nucleus. These were not found when the injection sites were confined to the principal trigeminal nucleus region. To identify the source of the projection to the levator motoneurons, we injected retrograde tracer into the oculomotor complex. Retrogradely labeled cells were confined to a narrow, dorsoventrally oriented cell population that lined the rostral edge of the principal trigeminal nucleus. Presumably these cells inhibit levator motoneurons, while other parts of the trigeminal sensory complex are activating orbicularis oculi motoneurons, when a blink is initiated by sensory stimuli contacting the face.

Macaque monkey trigeminal blink reflex circuits targeting orbicularis oculi motoneurons.

The trigeminal blink reflex plays an important role in protecting the corneal surface from damage and preserving visual function in an unpredictable environment. The closing phase of the human reflex, produced by activation of the orbicularis oculi (ObOc) muscles, consists of an initial, small, ipsilateral R1 component, followed by a larger, bilateral R2 component. We investigated the circuitry that underlies this reflex in macaque (Macaca fascicularis and Macaca mulatta) monkeys by the use of single and dual tracer methods. Injection of retrograde tracer into the facial nucleus labeled neurons in the principal trigeminal nucleus, and in the spinal nucleus pars oralis and interpolaris, bilaterally, and in pars caudalis, ipsilaterally. Injection of anterograde tracer into the principal trigeminal nucleus labeled axons that directly terminated on ObOc motoneurons, with an ipsilateral predominance. Injection of anterograde tracer into pars caudalis of the spinal trigeminal nucleus labeled axons that directly terminated on ipsilateral ObOc motoneurons. The observed pattern of labeling indicates that the reticular formation ventromedial to the principal and spinal nuclei also contributes extensive bilateral input to ObOc motoneurons. Thus, much of the trigeminal sensory complex is in a position to supply a monosynaptic drive for lid closure, and the adjacent reticular formation can supply a disynaptic drive. These findings indicate that the assignment of the R1 and R2 components of the blink reflex to different parts of the trigeminal sensory complex cannot be exclusively based on subdivision connectional relationships with facial motoneurons. The characteristics of the R2 component may be due, instead, to other circuit properties.