Pigmented Rats Research Articles

Developmental changes in carbachol-stimulated inositolphosphate release in pigmented rat retina.

Carbachol-stimulated release of inositolphosphates (IP) was studied in the whole retina from Long-Evans rats of different ages (day 5, 10, 15, 20, adult) following in vitro incorporation of [3H]myo-inositol. Unlike the albino rat retina, the pigmented retina was highly light-sensitive, making it necessary to dark adapt the animals and perform retinal dissections under low illumination to prevent light-induced IP release. Retinae from postnatal day 10 rats showed the highest amount of carbachol-stimulated IP released. This response to carbachol decreased with age until postnatal day 20 when it reached adult levels. The pigmented rat retina showed a sharp fall in the degree of carbachol (1 mM)-stimulated IP released at the time of eye-opening (450% above basal in retinae from 10 day old animals, as compared to 230% above basal in 15 day old retinae). Basal release of IP was not altered in the retina during development. Muscarinic cholinergic receptor density was, however, found to increase 5 fold with age, reaching adult levels by PND 20. Retinal weight and protein per retina also increased (four fold) from day 5 to adult; however, the in vitro incorporation of [3H]myo-inositol into phosphoinositides (calculated as per mg protein) did not change during development. Thus, in animals prior to eye opening, a much higher proportion of phosphoinositides appears to be hydrolyzed upon muscarinic receptor stimulation. During retinal development a change in sensitivity to the agonist-sensitive pool(s) of phosphoinositides may occur and/or there may be alterations in the efficacy of receptor coupling to the second messenger system resulting in the disassociation observed between the drastic increase in receptor number and the apparent decrease in receptor-stimulated release of IP.

Fluorescein angiography as a means of assessing retinal vascular pathology in oxygen-exposed newborn rats.

Recently a new technique was reported in which examination of the retina of oxygen reared newborn rats was made using indirect fluorescence microscopy (Invest. Ophthal. Vis. Sci. 31:810). We have now improved this technique and systematically employed it as a means of studying oxygen-induced retinopathy in the newborn rat as an animal model for retinopathy of prematurity (ROP). Immediately after birth, litters of pigmented rats were exposed to an elevated oxygen atmosphere that varied in a cyclic fashion between 40% and 80% every 12 hours for 14 days. Rats raised simultaneously in room air served as controls. At the end of the treatment period, rats were deeply anesthetized, their pupils dilated, and 100 microliters of 3% sodium fluorescein was administered via tail venipuncture. After angiography, rats were awakened and returned to their mothers in room air for future assessment. Angiography was performed again at 4, 7, 38 or 56 days after oxygen treatment. Our results suggest that retinal pathology in the rat model parallels that of the human infant with ROP with respect to loss of patent retinal blood vessels in oxygen and subsequent abnormal vasoproliferation upon return to room air. Angiograms performed on room air-raised control rats at 14 days of age demonstrated our ability to resolve the smallest retinal capillaries. Angiograms conducted at the same age in oxygen-exposed rats revealed extensive areas of retinal non-perfusion and substantial arterio-venous shunting between adjacent primary vessels. If rats were maintained in room air for 4 or 7 days following oxygen exposure, a variety of pathologic signs became obvious including: 1) tortuosity of primary vessels mimicking human "plus disease", 2) frequent abnormal budding of tertiary vessels and capillaries, 3) retinal fluorescein leaks indicative of hemorrhages and 4) abnormal capillary tufts not evident at the time of removal from oxygen. By 38 and 56 days post-exposure, all four of these phenomena were still observed. Many of these pathologic phenomena could not have been observed with conventional methods currently used for retinal vascular assessment in small animals.

Spontaneous Gaze Shifts in Intact Head-free Rats and Following Inferior Olive and Cerebellar Lesions.

Recent experiments have shown that after lesions of the inferior olive or of the flocculus and paraflocculus of the cerebellum, in the pigmented rat, spontaneous saccades made when the head is completely restrained are followed by a large postsaccadic drift. The aims of the present paper were to study (i) the strategies and the characteristics of spontaneous eye - head coordinated gaze shifts in intact pigmented rats and to compare them with those described in other mammals, (ii) how they are affected by inferior olive and flocculus - paraflocculus lesions, and (iii) whether in these groups of animals the stability of the gaze is more deficient when the head is free to rotate in the horizontal plane (head-free condition) relative to the head-fixed condition. Three types of gaze shift strategy of intact rats are described and characterized. Following inferior olive or flocculus - paraflocculus lesion the dynamic parameters of such gaze shifts (the main sequences of head, gaze and eye and the timing of eye and head movement onset) are not significantly affected. The main deficits of lesioned animals affect the stability of gaze at the end of gaze shifts. After inferior olive lesion the amplitude of the postsaccadic drift of the gaze is 43.2% of the gaze saccade in the head-fixed condition, which is reduced to 22.9% in the head-free condition. Following flocculus - paraflocculus lesion the postsaccadic drift of gaze is even more reduced than after inferior olive lesion, changing from 39.2% in the head-fixed condition to only 9.7% in the head-free condition.

Visual thresholds in albino and pigmented rats.

Albino rats have recently been reported to have increment thresholds against dim backgrounds that are two log units higher than those of pigmented rats. We, on the other hand, have failed to confirm these differences using electroretinogram b-waves and pupillary light reflexes. This paper reports on experiments using evoked potentials from cortex and colliculus and single-unit recordings from colliculus. We recorded visual-evoked potentials from cortex and superior colliculus in the strains of albino (CD) and pigmented (Long-Evans) rats used in the earlier studies. Thresholds were determined on eight fully dark-adapted animals by extrapolating intensity-response curves to the point at which there was zero evoked potential. The average dark-adapted threshold for the visual-evoked cortical potential was -5.6 log cd/m2 in pigmented and -5.80 log cd/m2 in albino animals. The average dark-adapted threshold for the superior colliculus evoked response was -5.54 log cd/m2 in pigmented and -5.84 log cd/m2 in albinos. The differences were not statistically significant. On the same apparatus, the average absolute threshold for three human observers was -5.3 log cd/m2, a value close to the rat dark-adapted thresholds. Thus, visual-evoked cortical potentials and superior collicular evoked potentials failed to confirm the report of higher dark-adapted thresholds for albinos. In addition, we find that single units in superior colliculus in the albino rat respond to very dim flashes.

Ocular pharmacokinetics of trimetazidine in the pigmented rat after a single oral administration

Amoxicillin (AMX) is a widely used penicillin-type antibiotic whose presence in the environment has been widely investigated, despite its rapid hydrolysis to various degradation products (DPs). In this work, the formation of AMX DPs was studied in various aqueous solutions containing 100 μg mL−1 AMX. Three phosphate buffer solutions, at pH 5, pH 7 and pH 8, and a fourth buffer solution at pH 7 with the addition of the bivalent ions Mg2+and Ca2 as chelating agents, were examined under controlled environmental conditions. In addition, two solutions from natural sources were examined secondary effluents and tap water. The obtained DPs were identified by their MS/MS, UV and NMR spectra (obtained from pure compounds isolated by preparative HPLC) as: AMX penicilloic acid (ADP1/2), AMX penilloic acid (ADP4/5) and phenol hydroxypyrazine (ADP6). Two additional detected DPs AMX 2′,5′-diketopiperazine (ADP8/9), and AMX-S-oxide (ADP3) were reported and discussed in our previous publications. These DPs were then detected in secondary effluent and groundwater from a well located beneath agricultural fields continuously irrigated with secondary effluent. Concentrations in the secondary effluent were: ADP1/2, several micrograms per liter; ADP4/5, 0.15 μg L−1, and ADP8/9, 0.5 μg L−1. ADP6 were detected but not quantified. In the groundwater, only ADP8/9 was detected, at a concentration of 0.03 μg L−1. The detection and quantification of DPs of other investigated drugs is recommended as an integral part of any study, method or technique dealing with pharmaceutical residues in aquatic environments.

Synaptic ribbons, spheres and intermediate structures in the developing rat retina

The present study was conducted to investigate the qualitative and quantitative development of synaptic bodies in retinae of Wistar rats during postnatal days 4–28. In addition, the effects of different light regimens and of eye pigmentation on SB numbers were studied. Synaptic bodies were counted and measured in the outer plexiform layer of retinal tissue fixed and processed by routine electron microscopical techniques.At postnatal days 4 and 5, retinae showed only few synaptic bodies. The main numerical development of synaptic bodies occurred between postnatal days 4 and 9, numbers remaining more or less constant thereafter. The intracellular location of synaptic ribbons changed from predominantly cytoplasmic sites to positions at the membrane. In Wistar rats of postnatal day 15 held under a light/dark regimen, synaptic ribbon numbers and lengths were found to be significantly larger at night than at daytime. This was not observed in animals kept under constant darkness. In retinae of a pigmented rat strain, Brown Norway, total numbers of synaptic bodies were similar to those of Wistar rats, whereas the relative proportions of synaptic ribbons and spheres or sphere-like structures, respectively, differed between strains. These results are discussed with regard to synaptic body formation and regulation under the influence of light and eye pigmentation.

Effects of tone burst frequency and intensity on the auditory brainstem response (ABR) from albino and pigmented rats

Young adult male Sprague-Dawley (SC) and Long-Evans (LE) rats were evaluated using the auditory brainstem response (ABR). ABRs were evoked by stimuli with intensities ranging from 15 to 100 dB peSPL. Stimuli were tone bursts of 2000, 4000 and 8000 Hz. As stimulus intensity decreased from 100 to 15 dB, the ABR peak latencies prolonged, interpeak latencies (IPLs) shortened and amplitudes decreased. As stimulus frequency decreased from 8000 to 2000 Hz, ABR latencies prolonged, amplitudes decreased and ABR thresholds increased. The longest IPLs were in response to the 4000 Hz tone bursts. SD rats had ABRs with shorter peak latencies, larger amplitudes and lower thresholds than LE rats. The IPLs usually did not show significant strain-dependent differences. Our observations on stimulus intensity and frequency are consistent with previous reports. Our observations also suggest that the SD (albino) rat has better auditory acuity than the LE (pigmented) rat over the frequency range of 2000 to 8000 Hz. This implies that previous concerns about the use of albino animals in audiological research are somewhat overstated.

The cholinergic supersensitive pigmented rat—is it a better animal model for depression? : Gail Orpen, Meir Steiner St. Joseph's Hospital Research Institute, and McMaster University, Hamilton, Ontario, Canada

The cholinergic supersensitive pigmented rat—is it a better animal model for depression? : Gail Orpen, Meir Steiner St. Joseph's Hospital Research Institute, and McMaster University, Hamilton, Ontario, Canada

Laser-induced experimental vascular occlusion using liposome-encapsulated ADP.

The therapeutic occlusion of retinal vessels is often helpful in treating various pathological conditions. We compared the combined effects of argon laser photocoagulation and adenosine diphosphate (ADP) released from temperature-sensitive liposomes with argon laser photocoagulation alone on occlusion of retinal vessels in pigmented rats. In Group A, 8 eyes were treated with liposome-encapsulated ADP and laser photocoagulation. In Group B, 8 eyes were treated with laser photocoagulation alone. The laser parameters (power, spot size, exposure time) were maintained at the same levels for both groups. The laser was focused on the retinal vessels at the optic nerve head. The treated retinal vessels were observed at time zero, day 1, day 4, and weekly for a period of 3 months. At time zero, 6 of 8 eyes were totally occluded in Group A, with best results obtained at 80 mW. Only 1 of 8 eyes in Group B achieved total occlusion. After 3 months, 4 of 8 eyes in Group A remained totally occluded; no eyes in Group B were occluded. Complete and permanent occlusion of retinal vessels can be achieved by using ADP and laser photocoagulation of lower power density than traditional laser photocoagulation alone.

Possible Effect of Pigment on the Pharmacokinetics of Ofloxacin and Its Excretion in Hair

The mechanism of excretion of the antimicrobial ofloxacin in human scalp hair was investigated. When black and white hairs were taken from a patient with grizzled hair, who had been treated with ofloxacin, a much larger quantity of the drug was detected in the black hair. To study this difference and to elucidate the cause, ofloxacin (6,20, and 60 mg/kg/day, b.i.d.) was administered ip for 5 weeks to albino and pigmented rats, whose backs had been depilated beforehand. In the last week of administration, the time–plasma concentration profile of ofloxacin was determined. One week after the last dosing, the newly grown hair on the depilated area was collected, and the drug concentration in hair was measured. The concentration in hair of the pigmented rats correlated significantly with the daily dose, area under the plasma concentration curve (AUC), and maximum plasma concentration (Cmax) at steady state, whereas that in the albino rats correlated with the dose and Cmax only, because AUC did not increase linearly with the dose in the albino rats. Moreover, the drug concentration in the hair of the pigmented rats was always much larger than that in the hair of the albino ones, although AUC and Cmax did not differ greatly between both rat groups. The findings suggest that ofloxacin is excreted in the hair in relation to the dose administered, and that the mechanism of the excretion is closely linked with the presence of melanin.

Spatial organization of linear vestibuloocular reflexes of the rat: responses during horizontal and vertical linear acceleration

1. The spatial properties of linear vestibuloocular reflexes (LVOR) were studied in pigmented rats in response to sinusoidal linear acceleration on a sled. The orientation of the animal on the sled was altered in 15 degrees steps over the range of 360 degrees. Horizontal, vertical, and torsional components of eye movements were recorded with the magnetic field search coil technique in complete darkness. Conjugacy of the two eyes was studied in the horizontal movement plane. 2. Acceleration along the optic axis of one eye (approximately 50 degrees lateral) induced maximal vertical responses in the ipsilateral eye and, at the same time, maximal torsional responses in the contralateral eye. These vertical and torsional responses of the LVOR coincide with those obtained when the respective coplanar vertical semicircular canals are stimulated. Such a congruence suggests a common reference frame for LVOR and angular vestibuloocular reflexes (AVOR), with the result that direct combination of signals indicating apparent and real head tilt is facilitated. 3. Transformations of vertical and torsional responses into head coordinates (pitch and roll) show that these movements are compensatory in direction for any combination of apparent head tilt in pitch and roll planes. 4. Gain (rotation of the eye/apparent rotation of the gravity direction) was approximately 0.3 at 0.1 Hz and decreased to approximately 0.1 at 1.0 Hz. Vertical responses tended to have a larger gain than torsional responses. Phase lag relative to peak acceleration increased from about -9 degrees to about -47 degrees over the same frequency range. 5. Vertical linear acceleration evoked only vertical eye movements at a frequency of 1.0 Hz. 6. Horizontal responses of both eyes were symmetric or asymmetric in amplitude and in-phase (conjugate) or out-of-phase (disconjugate) with respect to each other, depending on the direction of linear acceleration. Translation in the transverse direction evoked conjugate compensatory horizontal responses. Forward-backward translation evoked movements of both eyes that were symmetric in amplitude, but 180 degrees out-of-phase. Translation along diagonal axes evoked almost no horizontal responses in the eye facing in the direction of linear motion but maximal horizontal responses in the eye facing away from the direction of linear motion. These disconjugate movements resulted in a modulation of the vergence angle of the eyes. 7. Disconjugate horizontal responses in darkness are best explained by the assumption that part of the visual consequences of a translational head displacement (i.e., change of viewing distance in light) is taken into account centrally.(ABSTRACT TRUNCATED AT 400 WORDS)

Horizontal optokinetic nystagmus in unilaterally enucleated pigmented rats: Role of the pretectal commissural fibers

Monocular enucleation reduces the asymmetry of horizontal optokinetic nystagmus (H-OKN) in afoveate mammals by increasing responses to naso-temporal visual stimulation. The origin of these larger responses was investigated in adult pigmented rats monocularly enucleated as neonates or as adults by analyzing retinal and commissural projections to the deafferented nucleus of the optic tract (NOT) and the functional role of this nucleus before and after section of the posterior commissure. Anatomically, monocular enucleation reduces the volume of the contralateral deafferented NOT. Anterograde tracers injected in the intact eye reveal a crossed projection of the retina to the NOT and to the dorsal (DTN) and medial (MTN) terminal nuclei of the accessory optic system as in normal rats. In addition, there is an uncrossed projection to the MTN in the rats enucleated as neonates. Retrograde tracer injected in the deafferented NOT confirms the absence of an uncrossed retinal projection but reveals connections between both NOT via the posterior commissure as in normal rats. Electrophysiologically, the larger naso-temporal optokinetic responses in monocularly enucleated rats return to normal after posterior commissurotomy. This study demonstrates that no anatomical remodelling takes place to increase naso-temporal responses in monocularly enucleated rats. The larger responses must then result from functional changes. The role of exclusive contralateral projections of the retina to the NOT and of the commissural connections in mediating the asymmetry of the optokinetic nystagmus in afoveate mammals is discussed.

Medial terminal nucleus terminals in the nucleus of the optic tract contain GABA: An electron microscopical study with immunocytochemical double labeling of GABA and PHA‐L

In this study the medial terminal nucleus (MTN) projection to the nucleus of the optic tract (NOT) was investigated in pigmented rats at the light and electron microscopical levels with a new combination of techniques. MTN terminals were anterogradely labeled with Phaseolus vulgaris-leucoagglutinin (PHA-L). Preembedding immunocytochemistry, followed by gold intensification, was used to visualize PHA-L. Postembedding immunocytochemistry with 15 nm immunogold particles was carried out to demonstrate the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Both PHA-L and GABA labeling can be easily discriminated at the electron microscopical level even when present in the same neuronal profiles. Light microscopically MTN-NOT fibers proved to have several branches with many varicosities. MTN terminals were found concentrated in terminal fields. Electron microscopically, it was shown that MTN boutons display characteristics resembling F-type terminals, i.e., terminals with dark mitochondria, pleomorphic vesicles, and symmetrical synapses. All NOT afferents originating from the MTN contained GABA and made multiple contacts exclusively with GABA negative NOT somata and dendrites. These results indicate the existence of a strong and direct inhibitory input onto GABA negative projection neurons in the NOT. This substantiates earlier physiological and morphological reports. It was further demonstrated that the location and organization of MTN terminals in the neuropil differ from that of the retinal input: MTN terminals are largely separated from retinal terminals. MTN terminal fields contain large amounts of GABA positive F terminals in contrast to retinal terminal areas. MTN terminals take part in irregularly shaped agglomerations of terminals, which contain many F terminals and dendritic processes and are surrounded by a glial sheet. Retinal terminals are found grouped together in small circular arrangements contacting a central dendrite.

The behavior of the homozygous and heterozygous sub-types of rats which are genetically-selected for diabetes insipidus: A comparison with Long Evans and Wistar stocks

Several aspects of spontaneous and conditioned behavior (food and water intake, locomotion and emotionality, passive and active avoidance acquisition and retention) of standard (albino and pigmented) rats, and rats heterozygous (HEDI) and homozygous (HODI) for diabetes insipidus, are reviewed. As would be expected, HODI rats have been repeatedly found to consume far more fluid than either HEDI or control rats. Pigmented rats appear to be more active than albinos. HODI rats exhibit less marked emotional responses than do control rats, among which the pigmented ones exhibit the highest emotionality. Light aversion is more evident in albino than in pigmented rats. No differences are found among HEDI, HODI and normal Long Evans rats. It is quite difficult to provide a clear-cut statement concerning inter-strain differences in passive avoidance behavior, possibly because of the variety of techniques employed. In any case, HODI rats do not perform worse than normal controls do. In one-way active avoidance paradigms, pigmented rats perform better than albinos, and the performance of HODI rats does not differ from that of controls. In two-way avoidance paradigms, albinos appear to outperform pigmented rats. Once again, there are no obvious differences between HODI and control animals. In addition to indicating that HODI rats may actually be less emotional than the other groups of rats reviewed here, the studies described once again fail to confirm the previously alleged functions of vasopressin in memory consolidation.

Adaptation and habituation of the vestibulo-ocular reflex in intact and inferior olive-lesioned rats

The gain of the vestibulo-ocular reflex (VOR) of intact pigmented rats was adaptively modified by training protocols that created a visual-vestibular conflict. For training, head restrained animals were oscillated on a turntable in front of an optokinetic pattern projected onto a cylindrical wall. The optokinetic pattern either moved the same amplitude with the animal ("in-phase": 0.05 Hz +/- 20 degrees/s) or opposite in direction ("out-of-phase": turntable and pattern 0.05 Hz +/- 10 degrees/s each). VOR responses were tested in darkness before and after each 8 min training period for a duration of 40 min. During "out-of-phase" training the gain of compensatory eye movements measured in light was close to 2 from the beginning on and the VOR tested in darkness increased in gain progressively from 0.48 (+/- 0.12) to 0.9 (+/- 0.3; P less than 0.05) in 5 out of 7 rats. Two rats did not adapt their VOR gain. Phase values decreased slightly by about 10 degrees. During "in-phase" stimulation compensatory eye movements were almost completely suppressed (gain close to 0) from the beginning on and the VOR tested in darkness decreased gradually in gain from 0.62 (+/- 0.17) to 0.13 (+/- 0.1; P less than 0.001) in all 6 trained rats. Phase values decreased in parallel from 151 degrees to 119 degrees (P less than 0.01). The effectiveness of the "in-phase" training paradigm in the absence of compensatory eye movements indicates that retinal image slip is the relevant signal for adaptation. In seven rats with histologically verified almost complete inferior olive (IO) lesions (chemically induced at least 45 days prior to training), "out-of-phase" and "in-phase" stimulation evoked compensatory eye movements with gains comparable to those in intact rats. VOR parameters measured in darkness were altered with respect to those of control rats. Gain differed extremely between individuals and phase lag re acceleration was in all IO-lesioned rats larger than in intact rats. The time constant of the VOR in response to table velocity steps was significantly longer (17 s +/- 4) than in intact rats (11 s +/- 3). Training did not alter the gain of the VOR in 5 out of 7 IO-lesioned rats. One rat increased its gain during "out-of-phase" training in the first, but not during a second training session (and not during "in-phase" training) and another rat decreased its gain during "in-phase" training (but not during "out-of-phase" training).(ABSTRACT TRUNCATED AT 400 WORDS)

Hexokinase Levels in Discrete Regions of Rat Brain: Evaluation by Quantitative Immuno fluoresence Using Interactive Laser Cytometry and Comparison with Basal Rates of Glucose Utilization

Relative levels of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) have been determined in 16 discrete regions of adult rat brain by a quantitative immunofluorescence method. The distribution of immunofluorescence in brain sections was determined by interactive laser cytometry and related to hexokinase content by comparison with standard sections containing known amounts of the enzyme. In many of these regions, referred to here as group I regions, hexokinase content was correlated with previously reported basal rates of glucose utilization. However, several regions (group II regions) in which hexokinase content exceeded that expected from basal rates of glucose utilization were also detected. Compared with the corresponding regions from albino rat brain, higher hexokinase levels were found in the dorsal and ventral lateral geniculate (group I regions) of pigmented Norway rats, a result reflecting previously reported increased glucose utilization by these regions in pigmented rats. There was no difference in hexokinase levels in the superior colliculus, a group II structure, from albino and pigmented rats, a finding implying that a reported increase in rate of glucose utilization in the superior colliculus of pigmented rats is effected without an increase in hexokinase content. It is suggested that group II regions may be adapted to sustain increases in rates of glucose utilization that are, relative to basal rates, considerably greater than those experienced by group I regions.

Are the differential effects of chloral hydrate on hooded rats vs. albino rats due to pigmentation or strain differences?

Effects of chloral hydrate anesthesia on EEG power spectra and VEP components were examined as a function of both pigmentation and strain differences in rats. Ten albino Westenberg Long Evans rats (WLE A) were compared to ten pigmented Westenberg Long Evans rats (WLE P), and to ten Wistar albino (Wis A) rats. Albino rats required less chloral hydrate to reach a deep level of anesthesia than pigmented rats. Wistar rats remained anesthetized longer than WLE rats. During deep levels of anesthesia, the lowest EEG frequency band contained more power in Wistar rats than in WLE rats. During moderate levels of anesthesia, frequencies less than 4 Hz lost power while frequencies greater than 13 Hz gained across all rats. Wistar rats had more power in the frequencies less than 8 Hz than did WLE rats; pigmented rats had more power in the frequencies greater that 13 Hz than did albinos. VEP component latencies of pigmented rats were shorter than albinos. Component amplitudes were not significantly different between groups.

Disruption of developmental timing in the albino rat retina

We have examined the spatial and temporal gradients of two developmental processes in albino and pigmented rats: outer plexiform layer (OPL) development, and rate of cell production. The OPL first appears as a thin, discontinuous break in the cytoblast layer that is frequently interrupted by the profiles of migrating neuro- and glioblasts. In both strains, this occurs in an area temporal to the optic disc that corresponds to the eventual site of peak ganglion cell density, but is not located along the line of nasotemporal division. The OPL is first evident at P5 in pigmented animals, but its appearance in albino animals is delayed approximately 30 hours, and its development appears to follow a flatter spatial gradient than in pigmented animals. In pigmented animals OPL formation is complete over most of the retina by P10, but in albino animals at this age it is yet to be completely formed at any retinal location. Reductions in mitotic activity are also first evident in temporal retina, but unlike OPL development, appear to follow the same temporal-spatial gradient in both strains. Reductions in temporal retina are obvious by P4, and mitotic activity has ceased altogether in midtemporal retina by P6 and throughout most remaining retinal regions by P8. Thus, the initial reduction of mitotic activity precedes the onset of OPL formation in both strains, but OPL development lags behind the reduction of mitotic activity to a greater extent in albino than in pigmented animals. Some aspects of differentiation within the inner nuclear layer (INL) were also examined. Just prior to the time of the onset of OPL formation, three distinct sublaminae are apparent in the INL. Cells in the innermost sublamina appear to be in an early stage of differentiation. Cells in the middle sublamina appear to be postmigratory, but have not yet begun to differentiate. Cells in the outermost sublamina have the appearance of migrating neuroblasts. At least some of these outer cells appear to migrate across the developing OPL to the outer nuclear layer, since the outermost sublamina becomes thinner and eventually disappears at the same time that the OPL becomes a continuous, uninterrupted plexiform layer. Cells of the middle sublamina apparently begin differentiation at about the time that this migration is complete. Although this sequence is the same in both albino and pigmented strains, its onset is delayed in albino animals by the same amount as the onset of OPL formation.(ABSTRACT TRUNCATED AT 400 WORDS)

The Influence of Visual and Somatosensory Input on the Vestibulo-Oculomotor Reflex of Pigmented Rats

Eye movements were recorded in the pigmented rat during vestibular, optokinetic and combined visual-vestibular stimulation. The dominant time constant in pigmented rats, tested during angular vestibular stimulation in darkness, is about two times longer than the cupular time constant. The gain and the duration of nystagmus, achieved by angular vestibular stimulation, can be enhanced by visual impulses. This is most evident during an optokinetic temporonasal stimulation, but is also seen with a nasotemporal stimulation. A mere optokinetic monocular stimulation without a synchronous vestibular excitation causes nystagmus only when the stimuli has a temporonasal direction. The duration of nystagmus, achieved by angular vestibular stimulation, is prolonged by disturbances of the neck proprioceptive system. This is more evident during a simultaneous visual input than in darkness. The ability to cancel nystagmus during conflicting vestibular and optokinetic impulses is well developed in the pigmented rat.

Evidence that the relative densities of afferents from both eyes control laminar distribution and binocular segregation of retinotectal projections in rats

In the superior colliculus of normal rodents the crossed retinal projection overlaps the uncrossed projection. The present study describes an abnormal laminar distribution and binocular segregation of the retinotectal afferents induced after the experimental enlargement of the uncrossed retinotectal pathway in pigmented rats. Intraocular injections of anterograde tracers were used to investigate the topographic and laminar organization of retinotectal projections in adult rats given unilateral optic tract lesions at birth. These lesions are known to increase the number of ipsilaterally projecting ganglion cells in the opposite retina. The uncrossed retinal projection to the remaining superior colliculus forms an abnormal band of terminal labeling at the superficial half of the stratum griseum superficiale, markedly different from the laminar distribution of this pathway in unoperated controls. This abnormal uncrossed projection has its maximum density at the rostrolateral quadrant of the tectum. Within this region, the crossed retinotectal projection retracts from the surface of the superior colliculus, leading to partial binocular segregation. The results suggest that both the laminar distribution and the experimental binocular segregation of retinotectal afferents depend on the balance of the densities of the converging pathways from both eyes in the superior colliculus.