Biomedical subjects

Michael J Mustari

Publications and source records attributed to Michael J Mustari.

13 recordsLinked to original sources

PubMed2006

Extraretinal signals in MSTd neurons related to volitional smooth pursuit.

Smooth pursuit (SP)-related neurons in the dorsal-medial part of medial superior temporal cortex (MSTd) carry extraretinal signals that may play a role in maintenance of SP once eye velocity matches target velocity. For example, it has not been determined whether the extraretinal signals reflect volitional SP commands or proprioception. The aim of this study was to test some potential sources of extraretinal signals in MSTd pursuit neurons. We tested 40 MSTd neurons during step-ramp SP with target blink conditions to show that they carried an extraretinal signal. To examine potential contributions from eye movements that might reflect proprioceptive feedback from eye muscles, we tested MSTd neurons during rotational vestibular ocular reflex in complete darkness (VORd). Vestibular stimulation was delivered in the earth horizontal plane to elicit reflex driven smooth eye movements that matched the speed and frequency of volitional SP. We also tested VOR in the light (VOR x 1) and cancellation of the VOR (VOR x 0). Our neurons were modulated during both SP and cancellation of the VOR. In contrast, MSTd smooth pursuit neurons with extraretinal signals were not significantly modulated during VORd (sensitivity < or = 0.10 spike/s/ degrees /s). This combination of properties is compatible with classifying these neurons as gaze-velocity related. Absence of modulation during VORd testing could be caused by cancellation of head and eye movement sensitivity or dependence of neuronal firing on volitional SP commands. Our results support the suggestion that modulation of SP-related MSTd neurons reflects volitional SP commands rather then eye movements generated by reflex pathways.

Animals↗

PubMed2005

Visual-vestibular interactions during vestibular compensation: role of the pretectal not in horizontal VOR recovery after hemilabyrinthectomy in rhesus monkey.

Damage to the vestibular labyrinth leads to profound nystagmus and vertigo. Over time, the vestibular-ocular system recovers in a process called vestibular compensation leading to reduced nystagmus and vertigo provided visual signals are available. Our study was directed at identifying sources of visual information that could play a role in vestibular compensation. Specifically, we investigated the role of the pretectal nucleus of the optic tract (NOT) in vestibular compensation after hemilabyrinthectomy (HL) in rhesus monkeys. We chose the NOT because this structure provides critical visual motion information for adaptive modification of the vestibular ocular reflex (VOR). We produced bilateral NOT lesions by injecting the excitotoxin ibotenic acid. We compared vestibular compensation after HL in NOT-lesioned and control animals with intact NOTs. We measured eye movements with an electromagnetic method employing scleral search coils. Measurements included slow-phase eye velocity during spontaneous nystagmus, per- and postrotatory nystagmus and the horizontal VOR (hVOR) gain (eye-velocity/head velocity) associated with per- and postrotatory and sinusoidal (0.2-2.0 Hz; 30-90 degrees/s) whole body oscillation around the earth-vertical axis. VOR gain was low (<0.5) for rotation toward the HL side. Our control animal evinced significant vestibular compensation with VOR gains approaching unity by 100 days post HL. In contrast, monkeys with bilateral lesions of the NOT never obtained this significant recovery with hVOR gains well below unity at 100 days and beyond. Therefore our studies demonstrate that the NOT is an essential source of visual signals for the process of vestibular compensation after HL.

Adaptation, Physiological↗

PubMed2005

Incomitance in monkeys with strabismus.

PURPOSE: Rhesus monkeys reared with restricted visual environment during their first few months of life develop large ocular misalignment (strabismus). The purpose of this study was to describe 'A and V' patterns and DVD in these animals during fixation and eye movements and suggest that this form of rearing produces animals that are suitable model to study the mechanisms that might cause 'A/V' pattern incomitant strabismus and dissociated vertical deviation (DVD) in humans. METHODS: Eye movements were recorded during fixation, smooth-pursuit and saccades using binocular search coils in one monkey with esotropia, three monkeys with exotropia and one normal monkey. RESULTS: 1) Monkeys reared with Alternating Monocular Occlusion or Binocular deprivation (tarsal plates intact) showed both horizontal and vertical misalignment during monocular and binocular viewing. 2) Large 'A' patterns were evident in 2 out of 3 exotropes while a 'V' pattern was observed in the esotrope. 3) Similar 'A/V' patterns were observed with either eye viewing and during fixation or eye movements. 4) The vertical misalignment, which consisted of the non-viewing eye being higher than the fixating eye, appeared to constitute a DVD. CONCLUSION: Visual sensory deprivation methods that induce large strabismus also induce 'A/V' patterns and DVD similar to certain types of human strabismus. The source of pattern strabismus could be central, i.e., altered innervation to extraocular muscles from motor nuclei, or peripheral, i.e., altered location of extraocular muscle pulleys.

Animals↗

PubMed2004

Discharge characteristics of pursuit neurons in MST during vergence eye movements.

For small objects moving smoothly in space close to the observer, smooth pursuit and vergence eye movements maintain target images near the foveae to insure high-resolution processing of visual signals about moving objects. Signals for both systems must be synthesized for pursuit-in-three-dimensions (3D). Recent studies have shown that responses of the majority of pursuit neurons in the frontal eye fields (FEF) code pursuit-in-3D. This area is known to have reciprocal connections with the medial superior temporal area (MST) where frontal pursuit neurons are found. To examine whether pursuit-in-3D signals are already present in MST and how MST neurons discharge during vergence-tracking induced by a small spot, we examined discharge of MST pursuit neurons in 2 monkeys. Of a total of 219 pursuit neurons examined during both frontal pursuit and vergence-tracking, 61% discharged only for frontal pursuit, 18% only for vergence-tracking, and 21% for both. A majority of vergence-related MST neurons exhibited sensitivity to vergence eye velocity. Their discharge was maintained during brief blanking of a vergence target. About 1/3 of vergence-related MST neurons exhibited visual responses to spot motion in depth. The preferred directions for visual motion and vergence-tracking were similar in half of our population. Some of the remaining neurons showed opposite preferred directions. A significant proportion (29%) of vergence-related neurons discharged before onset of eye movements with lead times longer than 20 ms. The results in this and previous studies indicate differences in discharge characteristics of FEF and MST pursuit neurons, suggesting different roles for the two in pursuit-in-3D.

Action Potentials↗

PubMed2004

Modeling of smooth pursuit-related neuronal responses in the DLPN and NRTP of the rhesus macaque.

The dorsolateral pontine nucleus (DLPN) and nucleus reticularis tegmenti pontis (NRTP) comprise obligatory links in the cortico-ponto-cerebellar system supporting smooth pursuit eye movements. We examined the response properties of DLPN and rNRTP neurons during step-ramp smooth pursuit of a small target moving across a dark background. Our neurophysiological studies were conducted in awake, behaving juvenile macaques (Macaca mulatta). We used multiple linear-regression modeling to estimate the relative sensitivities of neurons to eye parameters (position, velocity, and acceleration) and retinal-error parameters (position, velocity, and acceleration). We found that a large proportion of pursuit-related DLPN neurons primarily code eye-velocity information, whereas a large proportion of rNRTP neurons primarily code eye-acceleration information. We calculated the relative decrease in variance found when using a six-component model that included both eye- and retinal-error parameters compared with three-component models that include either eye or retinal error. These comparisons show that a majority of DLPN (14/20) and rNRTP (17/19) neurons have larger contributions from eye compared with retinal-error parameters (P < 0.001, paired t-test). Even though eye-motion parameters provide the strongest contributions in a given model, a significant contribution from retinal error was often present (i.e., >20% reduction in variance in 6-component model compared with 3-component models). Thus our results indicate that the DLPN plays a larger role in maintaining steady-state smooth pursuit eye velocity, whereas rNRTP contributes to both the initiation and maintenance of smooth pursuit.

Acceleration↗

PubMed2004

Gaze-related response properties of DLPN and NRTP neurons in the rhesus macaque.

The dorsolateral pontine nucleus (DLPN) and nucleus reticularis tegmenti pontis (NRTP) are basilar pontine nuclei important for control of eye movements. The aim of this study was to compare the response properties of neurons in DLPN and rostral NRTP (rNRTP) during visual, oculomotor, and vestibular testing. We tested 51 DLPN neurons that were modulated during smooth pursuit (23/51) or during motion of a large-field visual stimulus (28/51). Following vestibular testing, we found that the majority of smooth pursuit-related neurons in DLPN were best classified as gaze (13/23) or eye velocity (7/23) related. Only a small percentage (3/51) of DLPN neurons responded during vestibular ocular reflex in the dark (VORd). We tested rNRTP neurons as described above and found the majority of neurons (35/43) were modulated during smooth pursuit or during motion of a large-field stimulus only (4/43). A significant proportion of our rNRTP gaze velocity neurons (10/18) were also modulated during VORd. We found that the majority of smooth pursuit related neurons in rNRTP were best classified as gaze velocity (18/35) or gaze acceleration (11/35) sensitive. The remaining neurons were classified as eye position or eye/head related. We used multiple linear-regression modeling to determine the relative contributions of eye, head and visual inputs to the responses of DLPN and rNRTP neurons. Our results support the suggestion that both DLPN and rNRTP play significant roles not only in control of smooth pursuit but also in control of gaze.

Action Potentials↗

PubMed2004

Genome-wide transcriptional profiles are consistent with functional specialization of the extraocular muscle layers.

PURPOSE: Compartmentalization of the extraocular muscles into well-defined orbital and global layers is highly conserved. Recently, the active pulley hypothesis correlated the anatomic properties of orbital-global muscle layers with layer-specific division of labor. Microarray technology was used to identify muscle-layer-specific transcriptional profiles and, thereby, extend understanding of the structure-function characteristics of extraocular muscle layers. METHODS: Laser capture microdissection was used to obtain muscle layer samples from monkey medial rectus muscles. RNA was linearly amplified and hybridized to human U133 series microarrays (Affymetrix, Santa Clara, CA), which have sufficient sequence homology for use in subhuman primates. Data was analyzed using Affymetrix and Robust Multichip Average (RMA) algorithms. Select transcripts were verified by quantitative PCR and in situ hybridization. RESULTS: A broad spectrum of transcriptional differences (> 181 transcripts) was identified between the two extraocular muscle layers. Patterned differences in the sarcomeric contractile machinery and cytoskeleton were suggestive of key layer differences in contraction speed. Differentially expressed transcript identities, however, extended well beyond those traditionally associated with muscle-fiber-group differences. CONCLUSIONS: Muscle layer transcriptional profiles correlated with the different loads and usage patterns of extraocular muscle layers, as proposed in the active pulley hypothesis. The magnitude and breadth of orbital-global layer expression differences strongly suggests that oculomotor control systems may drive two distinct motor output pathways, each comprising separate motoneurons and muscle fibers, with one output path adapted to determining pulley position and the other to movement of the eye.

Animals↗

PubMed2003

Conjugate adaptation of saccadic gain in non-human primates with strabismus.

In this study, we have used the double-step paradigm to test saccadic gain adaptation during monocular viewing in one normal monkey, two monkeys with exotropia, and one monkey with esotropia. In this paradigm, the target for the saccade is displaced during the saccade, resulting in a consistent visual error. Studies in normal humans and monkeys have shown that the brain responds to this consistent visual error by gradually changing saccade gain. Using this technique, we were able to elicit adaptation in both the viewing eye and the nonviewing eye in the normal monkey and in monkeys with strabismus. The rate of adaptation was not significantly different in the viewing and nonviewing eyes in the normal and strabismic monkeys. The magnitude of adaptation as calculated by a percentage change in gain was also not significantly different in the viewing and the nonviewing eyes in the normal and strabismic monkeys. Our data show that animals with strabismus retain the ability to elicit a conjugate adaptation of saccades using this mechanism. We also suggest that the double-step paradigm elicits a conjugate adaptation of saccades whether the animal is viewing monocularly (our studies) or binocularly (data published in literature).

Adaptation, Physiological↗

PubMed2003

Role of the dorsolateral pontine nucleus in short-term adaptation of the horizontal vestibuloocular reflex.

The dorsolateral pontine nucleus (DLPN) is a major component of the cortico-ponto-cerebellar pathway that carries signals essential for smooth pursuit. This pathway also carries visual signals that could play a role in visually guided motor learning in the vestibular ocular reflex (VOR). However, there have been no previous studies that tested this possibility directly. The aim of this study was to determine the potential role of the DLPN in short-term VOR gain adaptation produced by viewing a scene through lenses placed in front of both eyes. In control experiments, adaptation of VOR gain was achieved by sinusoidal rotation (0.2 Hz, 30 degrees /s) for 2 h while the monkey viewed a stationary visual surround through either magnifying (x2) or minifying (x0.5) lenses. This led to increases (23-32%) or decreases (22-48%) of VOR gain as measured in complete darkness (VORd). We used injections of muscimol, a potent GABA(A) agonist (0.5 microl; 2%), to reversibly inactivate the DLPN, unilaterally, in three monkeys. After DLPN inactivation, initial acceleration of ipsilateral smooth-pursuit was reduced by 35-68%, and steady-state gain was reduced by 32-61%. Despite these significant deficits (P < 0.01) in ipsilesional smooth pursuit, the VOR during lens viewing was similar to that measured in preinjection control experiments. Similarly, after 2 h of adaptation, VORd gain was not significantly different (P > 0.61) from control adaptation values for either ipsi- or contralesional directions of head rotation. This was the case even though a stable ipsilesional smooth pursuit deficit persisted throughout the full adaptation period. Our results suggest that visual error signals for short-term adaptation of the VOR are derived from sources other than the DLPN perhaps including other basilar pontine nuclei and the accessory optic system.

Adaptation, Physiological↗

PubMed2003

Comprehensive evaluation of the extraocular muscle critical period by expression profiling in the dark-reared rat and monocularly deprived monkey.

PURPOSE: To address the consequences of visual deprivation paradigms in rat (dark rearing) and monkey (monocular deprivation) on extraocular muscle (EOM) development using genome-wide expression profiling. METHODS: Serial analysis of gene expression (SAGE) was used to determine alterations in the EOM transcriptome induced by dark rearing of rats from birth to postnatal day 45. Data were compared with previously published normal EOM SAGE library. DNA microarray similarly assessed changes in gene expression patterns of EOMs of monkeys reared from birth to 4 months of age with monocular deprivation. RESULTS: Dark rearing produced changes in expression of 280 transcripts in rat EOM. Of these, 71 were known genes representing functional categories that included energy metabolism/mitochondrial-related (21%), protein synthesis and modification (14%), lipid metabolism (13%), and muscle-related (6%) transcripts. Together, the predominant pattern reflected an energetic shift toward fatty acid beta-oxidation and integrated alterations in both myofibers and supportive tissues. The response of monkey rectus muscles to monocular deprivation was considerably less severe. CONCLUSIONS: The visual deprivation paradigms used in this study mimic alterations that are associated with the common disorders of strabismus, congenital cataract, and amblyopia. These data show that postnatal EOM maturation is broadly susceptible to changes in activity patterns that are a consequence of visuomotor maldevelopment. The data extend the concept of an EOM-critical period and establish that activity patterns in developing eye movement systems play vital determinant roles in the novel EOM phenotype.

Animals↗

PubMed2003

Role of the dorsolateral pontine nucleus in visual-vestibular behavior.

Visual-vestibular behavior depends on signals traveling in climbing and mossy fiber pathways. Our study examined the role of the dorsolateral pontine nucleus (DLPN), a major component of the cortico-ponto-cerebellar mossy fiber pathway. DLPN neurons discharge in relation to smooth pursuit and during visual stimulation, indicating a potential role in visually guided motor learning in the vestibulo-ocular reflex (VOR). We used unilateral muscimol injections to determine the potential role of the DLPN in short-term VOR gain adaptation. Preinjection adaptation of VOR gain was achieved by sinusoidal rotation (0.2 Hz, 30 degrees /s) for 2 h while the monkey viewed a stationary visual surround through either magnifying (x2) or minifying (x0.5) lenses. VOR gain increases (23-32%) or decreases (22-48%) as measured in complete darkness (VORd) were achieved. Following DLPN inactivation, initial acceleration of ipsilateral smooth-pursuit was reduced by 35-68%, and steady state gain was reduced by 32-61%. Furthermore, the monkey's ability to cancel the VOR was impaired. In contrast to these significant deficits in ipsilesional smooth pursuit, the VOR during lens viewing was similar to that measured in preinjection control experiments. Similarly, following 2 h of adaptation, VORd gain adaptation was indistinguishable from control adaptation values for either ipsilesional or contralesional directions of head rotation. Our results suggest that visual error signals for short-term adaptation of the VOR are derived from sources other than the DLPN, such as those from the accessory optic system.

Animals↗

PubMed2002

Cortical projections to the nucleus of the optic tract and dorsal terminal nucleus and to the dorsolateral pontine nucleus in macaques: a dual retrograde tracing study.

The nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT-DTN) along with the dorsolateral pontine nucleus (DLPN) have been shown to play a role in controlling slow eye movements and in maintaining stable vision during head movements. Both nuclei are known to receive cortical input from striate and extrastriate cortex. To determine to what degree this cortical input arises from the same areas and potentially from the same individual neurons, we placed different retrograde tracers into the NOT-DTN and the DLPN. In the ipsilateral cortical hemisphere the two projections mainly overlapped in the posterior part of the superior temporal sulcus (STS) comprising the middle temporal area (MT), the middle superior temporal area (MST), and the visual area in the fundus of the STS (FST) and the surrounding cortex. In these areas, neurons projecting to the NOT-DTN or the DLPN were closely intermingled. Nevertheless, only 3-11% of the labeled neurons in MT and MST were double-labeled in our various cases. These results indicate that the cortical input to the NOT-DTN and DLPN arises from largely separate neuronal subpopulations in the motion sensitive areas in the posterior STS. Only a small percentage of the projection neurons bifurcate to supply both targets. These findings are discussed in relation to the optokinetic and the smooth pursuit system.

Animals↗

PubMed2002

Animal models for visual deprivation-induced strabismus and nystagmus.

The development of gaze-stabilizing systems depends on normal vision during infancy. Monkeys reared with binocular lid suture (BLS) for the first 25-40 days of life have strabismus, optokinetic nystagmus deficits, latent nystagmus, and decreased binocular cells in the visual cortex and nucleus of the optic tract. When BLS is extended to 55 days, pendular and congenital nystagmus also occurs. Eyelids in infant monkeys are hairless and thin, but BLS still degrades sensory fusion, motion, and form perception. To determine to what extent these visual properties are critical in the development of normal gaze stabilization, we examined infant monkeys reared with one opaque contact lens over one eye, alternated to the fellow eye every other day (AMO); and monkeys reared in a 3-Hz strobe environment. Monkeys reared with AMO develop strabismus, but have normal optokinetic nystagmus and no spontaneous nystagmus. Area 17 is monocular, but the medial temporal area and the nucleus of the optic tract are binocular. Monkeys reared in strobe light develop pendular nystagmus but not strabismus. We were puzzled by the results of the AMO monkeys until we examined infant monkeys with BLS that were prevented from seeing form through the lids. This was done by leaving the tarsal plate intact behind the eyelid. They developed similar to the AMO monkeys. These results suggest that disruption of sensory fusion during infancy (BLS, AMO) causes strabismus. If strabismus occurs while the monkeys have some form vision from each eye (BLS without tarsal plate), then the nucleus of the optic tract becomes monocular, which causes optokinetic nystagmus deficits and latent nystagmus. Infant monkeys reared without visual motion develop pendular nystagmus.

Animals↗