Layers Of Lateral Geniculate Nucleus Research Articles

Parallel Streams of Direct Corticogeniculate Feedback from Mid-level Extrastriate Cortex in the Macaque Monkey.

First-order thalamic nuclei receive feedforward signals from peripheral receptors and relay these signals to primary sensory cortex. Primary sensory cortex, in turn, provides reciprocal feedback to first-order thalamus. Because the vast majority of sensory thalamocortical inputs target primary sensory cortex, their complementary corticothalamic neurons are assumed to be similarly restricted to primary sensory cortex. We upend this assumption by characterizing morphologically diverse neurons in multiple mid-level visual cortical areas of the primate (Macaca mulatta) brain that provide direct feedback to the primary visual thalamus, the dorsal lateral geniculate nucleus (LGN). Although the majority of geniculocortical neurons project to primary visual cortex (V1), a minority, located mainly in the koniocellular LGN layers, provide direct input to extrastriate visual cortex. These "V1-bypassing" projections may be implicated in blindsight. We hypothesized that geniculocortical inputs directly targeting extrastriate cortex should be complemented by reciprocal corticogeniculate circuits. Using virus-mediated circuit tracing, we discovered corticogeniculate neurons throughout three mid-level extrastriate areas: MT, MST, and V4. Quantitative morphological analyses revealed nonuniform distributions of unique cell types across areas. Many extrastriate corticogeniculate neurons had spiny stellate morphology, suggesting possible targeting of koniocellular LGN layers. Importantly though, multiple morphological types were observed across areas. Such morphological diversity could suggest parallel streams of V1-bypassing corticogeniculate feedback at multiple stages of the visual processing hierarchy. Furthermore, the presence of corticogeniculate neurons across visual cortex necessitates a reevaluation of the LGN as a hub for visual information rather than a simple relay.

Cell death in the lateral geniculate nucleus, and its possible relationship with nicotinic receptors and sudden infant death syndrome (SIDS)

The role of the lateral geniculate nucleus (LGN) in vision has been extensively studied, yet its extraretinal capacities are still being investigated, including its role in arousal from sleep. The β2 nicotinic acetylcholine receptor (nAChR) subunit is involved in the laminal organisation of the LGN with magnocellular (MC) and parvocellular (PC) neurons. Sudden infant death syndrome (SIDS) occurs during a sleep period and, neuropathologically, is associated with increased neuronal cell death and altered nAChRs. A recent qualitative pilot study from our group implicates the possibility of increased neuronal death/apoptosis in the SIDS LGN. The present study used quantitative analysis to report the baseline expression of apoptotic and nAChR subunits α7 and β2 in the PC and MC layers of the LGN, to determine correlations amongst these markers within layers and across layers, and to evaluate changes in the expression of these markers in the LGN of SIDS infants, along with associations with SIDS risk factors, such as age, sex, cigarette smoke exposure, bed-sharing, and presence of an upper respiratory tract infection (URTI). Tissue was immunohistochemically stained for cell death markers of active caspase-3 (Casp-3) and TUNEL, and for the α7 and β2 nAChR subunits. Amongst 43 cases of sudden and unexpected deaths in infancy (SUDI), classifications included explained deaths (eSUDI, n = 9), SIDS I (n = 5) and SIDS II (n = 29). Results indicated a strong correlation of the apoptotic markers and β2 nAChR subunit between the LGN layers, but not across the markers within the layers. Amongst the diagnostic groups, compared to eSUDI, the SIDS II cases had decreased Casp-3 expression while β2 nAChR expression was increased in both PC and MC layers. Amongst the SIDS risk factors, URTI and bed-sharing were associated with changes in neuronal death but not in the α7 and β2 markers. In conclusion, our findings do not support a role for the α7 and β2 nAChRs in apoptotic regulation of the LGN layers during infancy. However, for SIDS victims, an inverse correlation between the changes for markers of apoptosis and the β2 nAChR subunit expression suggests altered LGN function.

Structural Changes and Astrocyte Response of the Lateral Geniculate Nucleus in a Ferret Model of Ocular Hypertension.

We investigated structural changes and astrocyte responses of the lateral geniculate nucleus (LGN) in a ferret model of ocular hypertension (OH). In 10 ferrets, OH was induced via the injection of cultured conjunctival cells into the anterior chamber of the right eye; six normal ferrets were used as controls. Anterograde axonal tracing with cholera toxin B revealed that atrophic damage was evident in the LGN layers receiving projections from OH eyes. Immunohistochemical analysis with antibodies against NeuN, glial fibrillary acidic protein (GFAP), and Iba-1 was performed to specifically label neurons, astrocytes, and microglia in the LGN. Significantly decreased NeuN immunoreactivity and increased GFAP and Iba-1 immunoreactivities were observed in the LGN layers receiving projections from OH eyes. Interestingly, the changes in the immunoreactivities were significantly different among the LGN layers. The C layers showed more severe damage than the A and A1 layers. Secondary degenerative changes in the LGN were also observed, including neuronal damage and astrocyte reactions in each LGN layer. These results suggest that our ferret model of OH is valuable for investigating damages during the retina–brain transmission of the visual pathway in glaucoma. The vulnerability of the C layers was revealed for the first time.

Relation of koniocellular layers of dorsal lateral geniculate to inferior pulvinar nuclei in common marmosets.

Traditionally, the dorsal lateral geniculate nucleus (LGN) and the inferior pulvinar (IPul) nucleus are considered as anatomically and functionally distinct thalamic nuclei. However, in several primate species it has also been established that the koniocellular (K) layers of LGN and parts of the IPul have a shared pattern of immunoreactivity for the calcium-binding protein calbindin. These calbindin-rich cells constitute a thalamic matrix system which is implicated in thalamocortical synchronisation. Further, the K layers and IPul are both involved in visual processing and have similar connections with retina and superior colliculus. Here, we confirmed the continuity between calbindin-rich cells in LGN K layers and the central lateral division of IPul (IPulCL) in marmoset monkeys. By employing a high-throughput neuronal tracing method, we found that both the K layers and IPulCL form comparable patterns of connections with striate and extrastriate cortices; these connections are largely different to those of the parvocellular and magnocellular laminae of LGN. Retrograde tracer-labelled cells and anterograde tracer-labelled axon terminals merged seamlessly from IPulCL into LGN K layers. These results support continuity between LGN K layers and IPulCL, providing an anatomical basis for functional congruity of this region of the dorsal thalamic matrix and calling into question the traditional segregation between LGN and the inferior pulvinar nucleus.

Binocular summation in marmoset lateral geniculate nucleus.

In primates and carnivores, the main laminae of the dorsal lateral geniculate nucleus (LGN) receive monocular excitatory input in an eye-alternating fashion. There is also evidence that nondominant eye stimulation can reduce responses to dominant eye stimulation and that a subset of LGN cells in the koniocellular (K) layers receives convergent binocular excitatory input from both eyes. What is not known is how the two eye inputs summate in the K layers of LGN. Here, we aimed to answer this question by making extracellular array electrode recordings targeted to K layers in the marmoset (Callithrix jacchus) LGN, as visual stimuli (flashed 200 ms temporal square-wave pulses or drifting gratings) were presented to each eye independently or to both eyes simultaneously. We found that when the flashed stimulus was presented to both eyes, compared to the dominant eye, the peak firing rate of most cells (61%, 14/23) was reduced. The remainder showed response facilitation (17%) or partial summation (22%). A greater degree of facilitation was seen when the total number of spikes across the stimulus time window (200 ms) rather than peak firing rates was measured. A similar pattern of results was seen for contrast-varying gratings and for small numbers of parvocellular (n = 12) and magnocellular (n = 3) cells recorded. Our findings show that binocular summation in the marmoset LGN is weak and predominantly sublinear in nature.

C-FOS expression in the visual system of tree shrews after monocular inactivation.

Tree shrews possess an unusual segregation of ocular inputs to sublayers rather than columns in the primary visual cortex (V1). In this study, the lateral geniculate nucleus (LGN), superior colliculus (SC), pulvinar, and V1 were examined for changes in c-FOS, an immediate-early gene, expression after 1 or 24 hours of monocular inactivation with tetrodotoxin (TTX) in tree shrews. Monocular inactivation greatly reduced gene expression in LGN layers related to the blocked eye, whereas normally high to moderate levels were maintained in the layers that receive inputs from the intact eye. The SC and caudal pulvinar contralateral to the blocked eye had greatly (SC) or moderately (pulvinar) reduced gene expressions reflective of dependence on the contralateral eye. c-FOS expression in V1 was greatly reduced contralateral to the blocked eye, with most of the expression that remained in upper layer 4a and lower 4b and lower layer 6 regions. In contrast, much of V1 contralateral to the active eye showed normal levels of c-FOS expression, including the inner parts of sublayers 4a and 4b and layers 2, 3, and 6. In some cases, upper layer 4a and lower 4b showed a reduction of gene expression. Layers 5 and sublayer 3c had normally low levels of gene expression. The results reveal the functional dominance of the contralateral eye in activating the SC, pulvinar, and V1, and the results from V1 suggest that the sublaminar organization of layer 4 is more complex than previously realized. J. Comp. Neurol. 525:151-165, 2017. © 2016 Wiley Periodicals, Inc.

Analysis of the lateral geniculate nucleus in dichromatic and trichromatic marmosets.

Marmosets are diurnal New World monkeys that show sex-linked cone photopigment polymorphism, whereby all males and some females are dichromats ("red-green colorblind"), but most females show trichromatic color vision. Here we asked whether trichromats express chromatic-specific circuitry in the lateral geniculate nucleus (LGN). The volume of parvocellular (P), magnocellular (M), and koniocellular (K) layers was calculated in Nissl-stained sections from the LGN of adult marmosets (Callithrix jacchus; 10 trichromatic females; 2 dichromatic females; and 13 dichromatic males). Retinal ganglion cell axon terminals within the P and K layers were reconstructed and measured following anterograde tracer (dextran) injections. We show that there is little difference in LGN layer volume with respect to age, weight, or sex of the animals, or between dichromatic and trichromatic phenotypes. The morphology of retinal ganglion cell terminals was largely indistinguishable on comparing dichromats and trichromats, and likewise on comparing terminals representing peripheral or foveal retina. We conclude that the LGN circuits we studied are largely independent of red-green color vision phenotype and visual field location.

Weak orientation and direction selectivity in lateral geniculate nucleus representing central vision in the gray squirrel Sciurus carolinensis.

Classic studies of lateral geniculate nucleus (LGN) and visual cortex (V1) in carnivores and primates have found that a majority of neurons in LGN exhibit a center-surround organization, while V1 neurons exhibit strong orientation selectivity and, in many species, direction selectivity. Recent work in the mouse and the monkey has discovered previously unknown classes of orientation- and direction-selective neurons in LGN. Furthermore, some recent studies in the mouse report that many LGN cells exhibit pronounced orientation biases that are of comparable strength to the subthreshold inputs to V1 neurons. These results raise the possibility that, in rodents, orientation biases of individual LGN cells make a substantial contribution to cortical orientation selectivity. Alternatively, the size and contribution of orientation- or direction-selective channels from LGN to V1 may vary across mammals. To address this question, we examined orientation and direction selectivity in LGN and V1 neurons of a highly visual diurnal rodent: the gray squirrel. In the representation of central vision, only a few LGN neurons exhibited strong orientation or direction selectivity. Across the population, LGN neurons showed weak orientation biases and were much less selective for orientation compared with V1 neurons. Although direction selectivity was weak overall, LGN layers 3abc, which contain neurons that express calbindin, exhibited elevated direction selectivity index values compared with LGN layers 1 and 2. These results suggest that, for central visual fields, the contribution of orientation- and direction-selective channels from the LGN to V1 is small in the squirrel. As in other mammals, this small contribution is elevated in the calbindin-positive layers of the LGN.

Effects of senescence on the expression of BDNF and TrkB receptor in the lateral geniculate nucleus of cats.

To explore the neural mechanisms mediating aging-related visual function declines, we compared the expressions of brain-derived neurotrophic factor (BDNF) and its high affinity receptor-tyrosine kinase B (TrkB) between young and old adult cats. Nissl staining was used to display neurons in each layer of the lateral geniculate nucleus (LGN). The BDNF- and TrkB receptor-immunoreactive neurons were labeled immunohistochemically, observed under optical microscope and photographed. Their neuronal density and immunoreactive intensity were measured. Results showed that the mean density of the Nissl stained neurons in each LGN layer were comparable between old and young adult cats, and their BDNF and TrkB proteins were widely expressed in all LGN layers. However, compared with young adult cats, both the density and optical absorbance intensity of BDNF- and TrkB-immunoreactive cells in each LGN layer in old cats were significantly decreased. These findings indicate that the decreased expressions of BDNF and TrkB proteins in the LGN may be an important factor inducing the compromised inhibition in the central visual nucleus and the functional visual decline in senescent individuals.

Distinct patterns of corticogeniculate feedback to different layers of the lateral geniculate nucleus.

In primates, feedforward visual pathways from retina to lateral geniculate nucleus (LGN) are segregated to different layers. These layers also receive strong reciprocal feedback pathways from cortex. The degree to which feedforward streams in primates are segregated from feedback streams remains unclear. Here, we asked whether corticogeniculate cells that innervate the magnocellular (M), parvocellular (P), and koniocellular (K) layers of the LGN in the prosimian primate bush baby (Otolemur garnettii) can be distinguished based on either the laminar distribution or morphological characteristics of their axons and synaptic contacts in LGN, or on their cell body position, size, and dendritic distribution in cortex. Corticogeniculate axons and synapses were labeled anterogradely with biotinylated dextran injections in layer 6 of cortex. Corticogeniculate cell bodies were first labeled with fluorescent dextran injections limited to individual M, P, or K LGN layers and then filled with biotinylated Lucifer yellow. Results showed that feedback to the M or P LGN layers arises from cells with dendrites primarily confined to cortical layer 6 and axons restricted to either M or P LGN layers, but not both. Feedback to K LGN layers arises from cells: 1) whose dendrites distribute rather evenly across cortical layers 5 and 6; 2) whose dendrites always extend into layer 4; and 3) whose axons are never confined to K layers but always overlap with either P or M layers. Corticogeniculate axons also showed distributions that were retinotopically precise based on known receptive field sizes of layer 6 cells, and these axons mainly made synapses with glutamatergic projection neurons in the LGN in all layers. Taken together with prior physiological results, we argue that the morphological differences between the three corticogeniculate pathways show that the M and P feedback pathways could rapidly and specifically enhance local LGN activity, while we speculate that the K feedback pathway is organized to temporally synchronize activity between LGN and cortex.

Metabotropic glutamate receptor 5 shows different patterns of localization within the parallel visual pathways in macaque and squirrel monkeys.

Glutamate is used as an excitatory neurotransmitter by the koniocellular (K), magnocellular (M), and parvocellular (P) pathways to transfer signals from the primate lateral geniculate nucleus (LGN) to primary visual cortex (V1). Glutamate acts through both fast ionotropic receptors, which appear to carry the main sensory message, and slower, modulatory metabotropic receptors (mGluRs). In this study, we asked whether mGluR5 relates in distinct ways to the K, M, and P LGN axons in V1. To answer this question, we used light microscopic immunocytochemistry and preembedding electron microscopic immunogold labeling to determine the localization of mGluR5 within the layers of V1 in relation to the K, M, and P pathways in macaque and squirrel monkeys. These pathways were labeled separately via wheat germ agglutinin–horseradish peroxidase (WGA–HRP) injections targeting the LGN layers. mGluR5 is of interest because it: 1) has been shown to be expressed in the thalamic input layers; 2) appears to be responsible for some types of oscillatory firing, which could be important in the binding of visual features; and 3) has been associated with a number of sensory-motor gating-related pathologies, including schizophrenia and autism. Our results demonstrated the presence of mGluR5 in the neuropil of all V1 layers. This protein was lowest in IVCα (M input) and the infragranular layers. In layer IVC, mGluR5 also was found postsynaptic to about 30% of labeled axons, but the distribution was uneven, such that postsynaptic mGluR5 label tended to occur opposite smaller (presumed P), and not larger (presumed M) axon terminals. Only in the K pathway in layer IIIB, however, was mGluR5 always found in the axon terminals themselves. The presence of mGluR5 in K axons and not in M and P axons, and the presence of mGluR5 postsynaptic mainly to smaller P and not larger M axons suggest that the response to the release of glutamate is modulated in distinct ways within and between the parallel visual pathways of primates.

Functionally imaging the magno- and parvocellular layers of the human LGN during binocular rivalry

Introduction. Binocular rivalry occurs when conflicting images are presented to the eyes dichoptically. Rather than being perceived as one cohesive image, the two images compete for perceptual dominance, resulting in the images alternating in perceptual awareness. Neural explanations for this phenomenon have been debated; our interest was to determine the involvement of the magnocellular (M) and parvocellular (P) processing streams in rivalry. The lateral geniculate nucleus (LGN) is involved in dominance and suppression of visual input, consists of two ventral M layers and four dorsal P layers, and is the only place in the brain where these streams are spatially disjoint. Previous research has shown that activity in the LGN layers innervated by the suppressed eye is also suppressed during rivalry, but it is not clear whether both M and P streams are equally involved. Methods. Participants were scanned using a Siemens 3T MRI scanner. Functional EPI data were registered to a mean series of high-resolution proton density weighted images on which it is possible to measure the boundaries of the LGN and thus localize the M and P layers. Stimuli were presented through an Avotec binocular goggle system that allowed independent stimulation of each eye. The rivalrous stimuli were two rotating (1 Hz period) discs of high-contrast sinusoidal gratings that varied with regards to colour (red vs. green) and direction of rotation. Subjects held down a button to indicate which of the two stimuli was currently being perceived. Event-related averages were calculated from the functional data within the LGN. Results. The activation strengths of the M and P streams were compared. Both streams were found to participate equally in rivalry. Discussion. These results have implications for potential treatments for clinical disorders that result from M-cell deficits (e.g., dyslexia) and attentional disorders (e.g., attention deficit hyperactivity disorder, neglect syndromes). Meeting abstract presented at VSS 2013

Secondary Post-Geniculate Involvement in Leber’s Hereditary Optic Neuropathy

Leber’s hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR). Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN) in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P<0.05) and healthy subjects (P<0.01) in OR and not in the other brain regions. Increased OR diffusivity was associated with both disease duration (B = 0.002; P<0.05) and lack of recovery of visual acuity (B = 0.060; P<0.01). Post-mortem investigation detected atrophy (41.9% decrease of neuron soma size in the magnocellular layers and 44.7% decrease in the parvocellular layers) and, to a lesser extent, degeneration (28.5% decrease of neuron density in the magnocellular layers and 28.7% decrease in the parvocellular layers) in the LHON LGN associated with extremely severe axonal loss (99%) in the optic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons.

Plasticity and Stability of the Visual System in Human Achiasma

The absence of the optic chiasm is an extraordinary and extreme abnormality in the nervous system. The abnormality produces highly atypical functional responses in the cortex, including overlapping hemifield representations and bilateral population receptive fields in both striate and extrastriate visual cortex. Even in the presence of these large functional abnormalities, the effect on visual perception and daily life is not easily detected. Here, we demonstrate that in two achiasmic humans the gross topography of the geniculostriate and occipital callosal connections remains largely unaltered. We conclude that visual function is preserved by reorganization of intracortical connections instead of large-scale reorganizations of the visual cortex. Thus, developmental mechanisms of local wiring within cortical maps compensate for the improper gross wiring to preserve function in human achiasma.

An Alteration in the Lateral Geniculate Nucleus of Experimental Glaucoma Monkeys: In vivo Positron Emission Tomography Imaging of Glial Activation

We examined lateral geniculate nucleus (LGN) degeneration as an indicator for possible diagnosis of glaucoma in experimental glaucoma monkeys using positron emission tomography (PET). Chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty in the left eyes of 5 cynomolgus monkeys. Glial cell activation was detected by PET imaging with [11C]PK11195, a PET ligand for peripheral-type benzodiazepine receptor (PBR), before and at 4 weeks after laser treatment (moderate glaucoma stage). At mild, moderate, and advanced experimental glaucoma stages (classified by histological changes based on the extent of axonal loss), brains were stained with cresyl violet, or antibodies against PBR, Iba-1 (a microglial marker), and GFAP (an activated astrocyte marker). In laser-treated eyes, IOP was persistently elevated throughout all observation periods. PET imaging showed increased [11C]PK11195 binding potential in the bilateral LGN at 4 weeks after laser treatment; the increase in the ipsilateral LGN was statistically significant (P<0.05, n = 4). Immunostaining showed bilateral activations of microglia and astrocytes in LGN layers receiving input from the laser-treated eye. PBR-positive cells were observed in LGN layers receiving input from laser-treated eye at all experimental glaucoma stages including the mild glaucoma stage and their localization coincided with Iba-1 positive microglia and GFAP-positive astrocytes. These data suggest that glial activation occurs in the LGN at a mild glaucoma stage, and that the LGN degeneration could be detected by a PET imaging with [11C]PK11195 during the moderate experimental glaucoma stage after unilateral ocular hypertension. Therefore, activated glial markers such as PBR in the LGN may be useful in noninvasive molecular imaging for diagnosis of glaucoma.

Molecular compartmentalization of lateral geniculate nucleus in the gray squirrel (Sciurus carolinensis)

Previous research has suggested that the three physiologically defined relay cell-types in mammalian lateral geniculate nucleus (LGN)—called parvocellular (P), magnocellular (M), and koniocellular (K) cells in primates and X, Y, and W cells in other mammals—each express a unique combination of cell-type marker proteins. However, some of the relationships among physiological classification and protein expression found in primates, prosimians, and tree shrews do not apply to carnivores and murid rodents. It remains unknown whether these are exceptions to a common rule for all mammals, or whether these relationships vary over a wide range of species. To address this question, we examined protein expression in the gray squirrel (Sciurus carolinensis), a highly visual rodent. Unlike many rodents, squirrel LGN is well laminated, and the organization of X-like, Y-like, and W-like cells relative to the LGN layers has been characterized physiologically. We labeled tissue sections through visual thalamus with antibodies to calbindin and parvalbumin, the antibody Cat-301, and the lectin WFA. Calbindin expression was found in W-like cells in LGN layer 3, just adjacent to the optic tract. These results suggest that calbindin is a common marker for the konicellular pathway in mammals. However, while parvalbumin expression characterizes P and M cells in primates and X and Y cells in tree shrews, here it identifies only about half of the X-like cells in LGN layers 1 and 2. Putative Y/M cell markers did not differentiate relay cells in this animal. Together, these results suggest that protein expression patterns among LGN relay cell classes are variable across mammals.

Astrocytic responses in the lateral geniculate nucleus of monkeys with experimental glaucoma

To investigate the responses of lateral geniculate nucleus (LGN) astrocytes to experimental glaucoma in monkeys. Rhesus monkeys (Macaca mulatta). Unilateral chronic elevation of intraocular pressure (IOP) was induced in six rhesus monkeys by laser photocoagulation of the trabecular meshwork. Four normal monkeys were used as controls. Immunohistochemistry with antibodies to glial fibrillary acidic protein (GFAP), S100β and parvalbumin was used to specifically label astrocytes and neurons in the LGN. The relative immunointensity (RI) of GFAP was defined as the ratio of intensity between each region of interest to a reference field and compared between the experimental and control groups as a function of percentage optic nerve fiber loss. Ultrastructural changes of LGN astrocytes were examined by transmission electron microscopy. An increase in GFAP and S100β immunoreactivity was observed in the LGN layers receiving projections from the experimental glaucoma eyes. Quantitative analysis revealed that the RI of GFAP in both the magnocellular and parvocellular layers connected to the glaucomatous eyes increased in a linear fashion with increasing optic nerve fiber loss. Compared to controls, the RI of GFAP was also moderately elevated in LGN layers connected to the fellow nonglaucomatous eyes. Ultrastructurally, accumulation of glial filaments that occurred throughout the perikaryon and extended into the process in reactive astrocytes was observed in LGN layers of glaucomatous monkeys. Reactive astrogliosis occurs in the magnocellular and parvocellular LGN layers of monkeys with unilateral glaucoma. Astrocytes may play an important role in the regulation of LGN microenvironment in glaucoma.

VGLUT2 mRNA and protein expression in the visual thalamus and midbrain of prosimian galagos (Otolemur garnetti)

Vesicular glutamate transporters (VGLUTs) control the storage and presynaptic release of glutamate in the central nervous system, and are involved in the majority of glutamatergic transmission in the brain. Two VGLUT isoforms, VGLUT1 and VGLUT2, are known to characterize complementary distributions of glutamatergic neurons in the rodent brain, which suggests that they are each responsible for unique circuits of excitatory transmission. In rodents, VGLUT2 is primarily utilized in thalamocortical circuits, and is strongly expressed in the primary sensory nuclei, including all areas of the visual thalamus. The distribution of VGLUT2 in the visual thalamus and midbrain has yet to be characterized in primate species. Thus, the present study describes the expression of VGLUT2 mRNA and protein across the visual thalamus and superior colliculus of prosimian galagos to provide a better understanding of glutamatergic transmission in the primate brain. VGLUT2 is strongly expressed in all six layers of the dorsal lateral geniculate nucleus, and much less so in the intralaminar zones, which correspond to retinal and superior collicular inputs, respectively. The parvocellular and magnocellular layers expressed VGLUT2 mRNA more densely than the koniocellular layers. A patchy distribution of VGLUT2 positive terminals in the pulvinar complex possibly reflects inputs from the superior colliculus. The upper superficial granular layers of the superior colliculus, with inputs from the retina, most densely expressed VGLUT2 protein, while the lower superficial granular layers, with projections to the pulvinar, most densely expressed VGLUT2 mRNA. The results are consistent with the conclusion that retinal and superior colliculus projections to the thalamus depend highly on the VGLUT2 transporter, as do cortical projections from the magnocellular and parvocellular layers of the lateral geniculate nucleus and neurons of the pulvinar complex.

Morphological changes in the visual pathway induced by experimental glaucoma in Japanese monkeys

Glaucoma, an optic neuropathy, is the leading cause of world blindness. In this condition, the damage extends from the retina to the visual center in the brain, although the primary region of damage is thought to be the optic nerve head (ONH), with the lateral geniculate nucleus (LGN) being secondarily affected. We investigated time-dependent alterations in the ONH, the optic nerve (ON), and the LGN after intraocular pressure (IOP) elevation in Japanese monkeys (a species more similar to humans than other macaque species). Nine Japanese monkeys, each with an experimental glaucomatous left eye, and two naive monkeys were studied. Ocular-testing sessions (including IOP measurement and fundus photography) were held weekly. Eyes and brains were enucleated at 2–48 weeks after IOP elevation, and alterations in ONs and LGN were evaluated. The IOP of the treated eyes was monitored periodically and found to be elevated continuously throughout the observation period in each monkey. The ONH of the glaucomatous eyes exhibited time-dependent deep cupping and thinning of the rim area from 2 weeks after the IOP elevation. Loss of axons and a decrease in the area of ON were first observed at 4 and 28 weeks, respectively. Neuronal loss was first observed at 2 weeks in layers 1 and 2 of LGN [magnocellular (M)-layer] and at 12 weeks in layers 3–6 of LGN [parvocellular (P)-layer]. Neuronal shrinkage was first observed at 2 weeks in all layers in LGN. These findings indicate that in Japanese monkeys, damage to neurons in LGN can be detected in the early phase (first few weeks) after an IOP elevation, as can damage to ONH.

Whole-brain expression analysis of FMRP in adult monkey and its relationship to cognitive deficits in fragile X syndrome

Fragile X syndrome (FXS) is one of the most prevalent forms of heritable mental retardation and developmental delay in males. The syndrome is caused by the silencing of a single gene ( fragile X mental retardation- 1; FMR1) and the lack of expression of its protein product ( fragile X mental retardation-1 protein; FMRP). Recent work has linked the high expression levels of FMRP in the magnocellular layers of lateral geniculate nucleus (M-LGN) of the visual system to a specific reduction of perceptual function known to be mediated by that neural structure. This finding has given rise to the intriguing notion that FMRP expression level may be used as an index of susceptibility of specific brain regions to the observed perceptual and cognitive deficits in FXS. We undertook a comprehensive expression profiling study of FMRP in the monkey to obtain further insight into the link between FMPR expression and the behavioural impact of its loss in FXS. We report here the first 3D whole-brain map of FMRP expression in the Old-World monkey and show that certain brain structures display high FMRP levels, such as the cerebellum, striatum, and temporal lobe structures. This finding provides support for the notion that FMRP expression loss is linked to behavioural and cognitive impairment associated with these structures. We argue that whole-brain FMRP expression mapping may be used to formulate and test new hypotheses about other forms of impairments in FXS that were not specifically examined in this study.