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

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.

Although the core functions and structure of the lateral geniculate nucleus (LGN) are well understood, this core is surrounded by questions about the integration of feedforward and feedback connections, interactions between different channels of information, and how activity dependent development restructures synaptic networks. Our understanding of the organization of the mouse LGN is particularly limited given how important it has become as a model system. Advances in circuit scale electron microscopy (cellular connectomics) have made it possible to reconstruct the synaptic connectivity of hundreds of neurons within in a circuit the size of the mouse LGN. These circuit reconstructions can reveal cell type-to-cell type canonical wiring diagrams as well as the higher order wiring motifs that are only visible in reconstructions of intact networks. Connectomic analysis of the LGN therefore not only can answer longstanding questions about the organization of the visual thalamus but also presents unique opportunities for investigating fundamental properties of mammalian circuit formation.

Often mislabeled as a simple relay of sensory information, the thalamus is a complicated structure with diverse functions. This diversity is exemplified by roles visual thalamus plays in processing and transmitting light-derived stimuli. Such light-derived signals are transmitted to the thalamus by retinal ganglion cells (RGCs), the sole projection neurons of the retina. Axons from RGCs innervate more than ten distinct nuclei within thalamus, including those of the lateral geniculate complex. Nuclei within the lateral geniculate complex of nocturnal rodents, which include the dorsal lateral geniculate nucleus (dLGN), ventral lateral geniculate nucleus (vLGN), and intergeniculate leaflet (IGL), are each densely innervated by retinal projections, yet, exhibit distinct cytoarchitecture and connectivity. These features suggest that each nucleus within this complex plays a unique role in processing and transmitting light-derived signals. Here, we review the diverse cytoarchitecture and connectivity of these nuclei in nocturnal rodents, in an effort to highlight roles for dLGN in vision and for vLGN and IGL in visuomotor, vestibular, ocular, and circadian function.

Visual information reaches the cerebral cortex through a major thalamocortical pathway that connects the lateral geniculate nucleus (LGN) of the thalamus with the primary visual area of the cortex (area V1). In humans, ∼3.4 million afferents from the LGN are distributed within a V1 surface of ∼2400 mm2, an afferent number that is reduced by half in the macaque and by more than two orders of magnitude in the mouse. Thalamocortical afferents are sorted in visual cortex based on the spatial position of their receptive fields to form a map of visual space. The visual resolution within this map is strongly correlated with total number of thalamic afferents that V1 receives and the area available to sort them. The ∼20,000 afferents of the mouse are only sorted by spatial position because they have to cover a large visual field (∼300 deg) within just 4 mm2 of V1 area. By contrast, the ∼500,000 afferents of the cat are also sorted by eye input and light/dark polarity because they cover a smaller visual field (∼200 deg) within a much larger V1 area (∼400 mm2), a sorting principle that is likely to apply also to macaques and humans. The increased precision of thalamic sorting allows building multiple copies of the V1 visual map for left/right eyes and light/dark polarities, which become interlaced to keep neurons representing the same visual point close together. In turn, this interlaced arrangement makes cortical neurons with different preferences for stimulus orientation to rotate around single cortical points forming a pinwheel pattern that allows more efficient processing of objects and visual textures.

We studied the functional connectivity of cells in the lateral geniculate nucleus (LGN) with the primary visual cortex (V1) in anesthetized marmosets (Callithrix jacchus). The LGN sends signals to V1 along parallel visual pathways called parvocellular (P), magnocellular (M), and koniocellular (K). To better understand how these pathways provide inputs to V1, we antidromically activated relay cells in the LGN by electrically stimulating V1 and measuring the conduction latencies of P (n = 7), M (n = 14), and the “Blue-ON” (n = 5) subgroup of K cells (K-BON cells). We found that the antidromic latencies of K-BON cells were similar to those of P cells. We also measured the response latencies to high contrast visual stimuli for a subset of cells. We found the LGN cells that have the shortest latency of response to visual stimulation also have the shortest antidromic latencies. We conclude that Blue color signals are transmitted directly to V1 from the LGN by K-BON cells.

The histaminergic innervation of the thalamic dorsal and ventral lateral geniculate nuclei and the perigeniculate nucleus of the cat was examined immunohistochemically by means of an antibody to histamine.

We find histamine-immunoreactive neurons in the cat brain are concentrated in the ventrolateral portion of the posterior hypothalamus, confirming a previous report. However, this cell group also spreads into medial, dorsal, and extreme lateral regions of the posterior hypothalamus and extends as far rostral as the optic chiasm.

Histamine-labeled fibers cover all regions of the lateral geniculate complex, but the density of labeling varies. The ventral lateral geniculate nucleus (vLGN) is most densely labeled, the A laminae of the dorsal lateral geniculate are sparsely labeled, and the geniculate C laminae and the perigeniculate nucleus show intermediate amounts of label. Thus, histaminergic fibers demonstrate a predilection for zones innervated by the W-cell system. Labeled fibers exhibit few branchings and numerous en passant swellings, lending a beaded appearance. The vLGN showed more instances of fibers with larger-sized swellings (up to 2 μm).

Following injections of biotinylated tracers into the hypothalamus, we find labeled fibers throughout the lateral geniculate complex. The anterogradely labeled fibers resemblethe histaminergic fibers in morphology, distribution, and relative bouton size. Thus, the hypothalamus appears to be the source of the histaminergic fibers in the lateral geniculate complex.

Histamine-labeled fibers in the dorsal lateral geniculate nucleus (dLGN) exhibit uncommon ultrastructural morphology. Many extremely large, round, or elliptical vesicles fill the fiber swellings. Swellings are directly apposed to a variety of other dendritic and axonal profiles, but thus far no convincing synaptic contacts have been seen. The distribution and appearance of these histaminergic fibers resembles those reported for serotonergic fibers.

Our results support the idea that histamine works nonsynaptically as a neuromodulator in the lateral geniculate complex, affecting the level of visual arousal.

Axons containing serotonin (5-hydroxytryptamine, 5-HT) in the lateral geniculate nucleus of Macaca monkeys were stained using light or electron microscopic (EM) immunocytochemical labeling techniques. 5-HT labeled axons were sparsely and homogeneously distributed throughout the entire nucleus. Small varicosities were located irregularly along each axon giving them a beaded appearance. Examination of these axons at the EM level revealed that the varicosities contained synaptic vesicles that were variable in size and shape. Nearly all of the varicosities lacked synaptic contacts; only two out of over two hundred labeled varicosities appeared to form a synaptic contact, and serial sections through ten varicosities showed no discernible pre- or postsynaptic membrane specializations. 5-HT labeled axon varicosities were not observed to be preferentially located in proximity to any specific neuronal structures at either the light or EM level. 5-HT varicosities were estimated to form about 1% of the profiles containing synaptic vesicles in the neuropil of the lateral geniculate nucleus.

We conclude that axons containing serotonin in the lateral geniculate nucleus release this neurotransmitter to act in a neuromodulatory manner throughout the neuropil, probably to set a general level of neuronal excitability.

The distribution of neurons and fibers immunoreactive (ir) to the three calcium-binding proteins parvalbumin (PV), calbindin D-28k (CB), and calretinin (CR) was studied in the human lateral geniculate nucleus (LGN), lateral inferior pulvinar, and optic radiation, and related to that in the visual cortex. In the LGN, PV, CR, and CB immunoreactivity was present in all laminae, slightly stronger in the magnocellular than in the parvocellular laminae for CB and CR. PV-ir puncta, representing transversally cut axons, and CR-ir fibers were revealed within the laminae and interlaminar zones, and just beyond the outer border of lamina 6 in the geniculate capsule. In the optic radiation both PV- and CR-immunoreactive neurons, puncta, and fibers were present. CB immunoreactivity was revealed in neurons of all laminae of the lateral geniculate nucleus, including S lamina and interlaminar zones. There were hardly any CB-ir puncta or fibers in the laminae, interlaminar zones, geniculate capsule, or optic radiation. In the lateral inferior pulvinar, immunoreactive neurons for the three calcium-binding proteins were present in smaller number than in the LGN, as well as PV-ir puncta and CR-ir fibers within the nucleus and in the pulvinar capsule. In the white matter underlying area 17, fibers intermingled with a few scattered neurons were stained for both PV and CR, but very rarely for CB. These fibers stopped at the limit between areas 17 and 18. Area 17 showed a dense plexus of PV-ir puncta and neurons in the thalamo-receptive layer IV and CR-ir puncta and neurons both in the superficial layers I-II, IIIC, and in layer VA. Cajal-Retzius CR-ir neurons were present in layer I. CB-ir puncta were almost confined to layer I-III and CB-ir neurons to layer II. Finally the superior colliculus exhibited mostly populations of PV and CR pyramidal-like immunoreactive neurons, mainly in the intermediate tier. These data suggest that in the visual thalamus most calcium-binding protein immunoreactive neurons project to the visual cortex, while in the superior colliculus a smaller immunoreactive population represent projection neurons.

Studies of the numbers of retinal ganglion cells and lateral geniculate nucleus (LGN) neurons in primates suggest that the numbers of both types of neurons may vary over a two-fold range from one individual to another. This raises the question of whether the numbers of ganglion cells and LGN neurons are related or vary independently from individual to individual. We used stereological procedures to obtain unbiased estimates of the numbers of both cell types in seven rhesus monkeys. We found no significant correlation (rs. = −0.21) between the numbers of retinal and LGN cells in the same animals. In agreement with previous studies, the average ratio of the number of retinal ganglion cells that project to the LGN and the number of LGN cells was approximately 1:1. However, this ratio varied over a two-fold range, from 0.78:1 to 1.64:1, in individual animals. These results have important implications for understanding the mechanisms of retino-geniculate development and for understanding the connectional wiring between the retina and LGN.

Partial lesions of striate cortex were made in newborn and adolescent or young adult macaque monkeys, one newborn squirrel monkey, and adult squirrel and owl monkeys. After survival times ranging from 3 1/2 weeks to 8 years, the retinas were examined for transneuronal retrograde ganglion cell loss and retinal projections to the dorsal lateral geniculate nucleus, and other targets were examined for changes. After lesions in infant macaque monkeys and long postoperative survivals, nearly 80% of the ganglion cells were lost in the altered portions of the retinas. The degeneration appeared to be exclusively of ganglion cells projecting to the parvocellular layers of the lateral geniculate nucleus, and the loss of this class of cell appeared to be complete or nearly complete for the affected portions of the retina. Cases with shorter survivals showed that nine-tenths of the potential loss occurred within 6 months, and about half of the potential loss took place within one month. In cases where lesions were placed in adolescent and young adult macaque monkeys, the loss also was of ganglion cells projecting to the parvocellular layers. However, the rate of cell loss was slower so that little or no cell loss was apparent after six months, and only one-third to three-fourths of the potential loss occurred within 12–14 months. A cell loss of 22% was measured in the altered portions of the retina of a squirrel monkey lesioned as an infant and surviving for 6 months, but no regions of ganglion cell loss were apparent in the retinas of owl and squirrel monkeys lesioned as adults and surviving as long as two or more years.

We conclude that nearly 80% of the ganglion cells project to the parvocellular layers in macaque monkeys, and that the ultimate survival of these ganglion cells depends on the presence of target neurons in the parvocellular layers. Age is important in that the loss of ganglion cells proceeds rapidly in infant macaque monkeys, but slowly in older animals. Infant New World monkeys, judging from one squirrel monkey, are also susceptible to ganglion cell loss, although apparently at a rate comparable to older macaque monkeys. Finally, adult New World monkeys do not appear to be susceptible to ganglion cell loss. These age and species differences in rates of loss and susceptibility to loss challenge a “sustaining collateral” hypothesis proposed earlier (Weller et al., 1979), and suggest alternatives and modifications.

The putative neural pacemaker controlling circadian rhythms in mammals is contained in the suprachiasmatic nuclei of the hypothalamus. These nuclei receive a projection, the geniculo-hypothalamic tract (GHT), from neurons in the intergeniculate leaflet (IGL) and portions of the ventral lateral geniculate nucleus (vLGN) of the thalamus. We examined the responses of putative GHT neurons to diffuse illumination using extracellular electrophysiological recordings. The great majority of IGL neurons showed sustained ON responses to diffuse retinal illumination; vLGN neurons showed more variation in their responses. Discharge rates of sustained ON neurons increased monotonically as light intensity was increased and saturated over 2–3 log units of intensity changes. Many IGL neurons had binocular input, and input from the ipsilateral eye was often inhibitory. These results indicate that GHT neurons may provide information about ambient light intensity to the suprachiasmatic nuclei.

Recent investigations have shown that cortical nerve growth factor (NGF) infusions during the critical period inhibit ocular-dominance plasticity in the binocular portion of the rat visual cortex. The mechanisms underlying the effects of NGF on visual cortical plasticity are still unclear. To investigate whether during normal development intracortical and/or extracortical cells possess uptake/transport mechanisms for the neurotrophin, we injected 125I-NGF into the occipital cortex of rats at different postnatal ages. Within the cortex, only a few labelled cells were observed. These cells were confined to the vicinity of the injection site and their number depended on the animal's age at the time of injection. Labelled cells were absent at postnatal day (PD) 10 but could be detected between PD 14 and PD 18. They then decreased in number over the following period and were not detected in adult animals. Outside the cortex, neurons of the lateral geniculate nucleus (LGN) were not observed to take up and retrogradely transport NGF at any age after birth. In contrast, retrogradely labelled neurons were found in the basal forebrain. Labelled cells were first observed here at PD 14 and then increased in number until reaching the adult pattern. Our results show that intrinsic and extrinsic neurons are labelled following intracortical injections of iodinated NGF. In both neuronal populations, the uptake and transport of NGF is present over a period corresponding to the critical period for visual cortical plasticity. These findings suggest that NGF may play a role, both intra and extracortically, in plasticity phenomena.

Immunocytochemistry and retrograde labeling were used to define the thalamic projections of calbindin- and parvalbumin-containing cells in superficial layers of the rat's superior colliculus (SC). Quantitative analysis revealed that 90.8 ± 2.2% (mean ± standard deviation) of the calbindin-immunoreactive neurons in the stratum griseum superficiale (SGS) projected to the dorsal lateral geniculate nucleus (LGNd) and that 91.3 ± 4.3% of calbindin-immunoreactive neurons in the stratum opticum (SO) projected to the lateral posterior nucleus (LP). In contrast, only 17.3 ± 2.5% of parvalbumin-immunoreactive neurons in the SGS were found to project to the LGNd and 16.5 ± 3.1% of the parvalbumin-immunoreactive SO cells were retrogradely labeled after LP injections. Few of the parvalbumin-immunoreactive neurons in either the SGS (7.2 ± 2.5%) or the SO (9.2 ± 2.5%) were GABA positive. The retrograde-labeling results suggest that parvalbumin-immunoreactive neurons in the rat's SO and SGS may either be primarily interneurons or have descending projections, while calbindin-containing cells are primarily thalamic projection neurons. These results are consistent with data from other rodents, but almost exactly the opposite of data that have been reported for the cat for these same populations of SC projection neurons. Such interspecies differences raise questions regarding the functional importance of expressing one calcium-binding protein versus another in a specific neuronal population.

In this study we examine the postnatal development of retinogeniculate axons projecting to the magnocellular (M axons), parvocellular (P axons), and koniocellular (K axons) layers of the lateral geniculate nucleus (LGN) in the prosimian primate, Galago crassicaudatus, in order to: (1) understand how individual retinogeniculate axons in primates mature postnatally, and (2) determine whether differences exist in the development of separate classes of axons that are known to be presynaptic to physiologically distinct cells in adults. In galagos, magnocellular, parvocellular, and koniocellular LGN layers contain Y-, X-, and W-like physiological cell classes, respectively (Norton & Casagrande, 1982).

In vitro and in vivo optic tract bulk injections of horseradish peroxidase (HRP) were made in animals ranging in age from the day of birth (P0) to adulthood. Two hundred and fifty axonal arbors were completely reconstructed from serial sections and examined qualitatively for general features of maturity and compared quantitatively for changes in shape, arbor width, area, volume, bouton number, and bouton density.

Our results confirm that in adult galagos M arbors are large and radially symmetric; P arbors are medium sized and elongated perpendicular to layer borders; K arbors are small and generally oriented parallel to layer borders. At birth, M, P, and K arbors, although still distinct and confined to layers, are qualitatively and quantitatively immature. Both the pattern and pace of maturation differ between classes. Overall, M arbors mature before P arbors which in turn mature before K arbors. Within classes, arbors representing central vision appear to develop about a week ahead of those representing peripheral vision; no differences are evident between the development of crossed and uncrossed arbors. In no case do arbors exhibit a period of postnatal exuberance, wherein arbors are larger than those of the adult as reported for cat X retinal axons. However, in width and bouton density P arbors are mature at P0 and thus occupy relatively more space in the nucleus compared to adult. All arbors mature rapidly and appear adult-like by the 4th or 5th postnatal week.

Responses to full-field colored flashes (red, blue, and green) were compared with those to illuminancematched white flashes in area V1, optic radiations, and the lateral geniculate nucleus of two alert macaques. Laminar profiles of visual evoked potentials (VEPs), current source density, and multiunit activity were obtained using multicontact electrodes capable of sampling from all layers of cortex or lateral geniculate nucleus, simultaneously. In striate cortex, stimulation with colored flash enhanced transmembrane current flow dramatically in both layer 4c and the supragranular laminae. Stimulation with red evoked the largest enhancement in every electrode penetration. The mean peak amplitudes of current sinks evoked by red were 203% and 537% of those evoked by white light in layer 4c and the supragranular laminae, respectively. Color effects in VI were preceded by an initial epoch of wavelength-insensitive activity. In layer 4c, the red effect reached significance, on average, at 47 ms, or ≈24 ms after the onset of transmembrane current flow. In the supragranular layers, the red effect reached significance, on average, at 55 ms, or ≈14 ms after the onset of current flow. Recordings from optic radiations in the white matter below V1 and from lateral geniculate nucleus showed no significant difference in the responses to color and illuminance-matched white light. Enhancement of supragranular current flow with color stimulation increased the contribution of these laminae to the generation of the surface VHP. Comparison of the surface VHP wave forms evoked by white and color stimuli may, therefore, help to differentiate the responses of the granular and supragranular laminae.

The response vs. contrast characteristics of different cell classes in the dorsal lateral geniculate nucleus (LGN) were compared. The luminance of a stationary flashing light spot was varied stepwise while the background luminance was constant. Lagged X cells had lower slope of the response vs. contrast curve (contrast gain), and they reached the midpoint of the response range over which the cells' response varied (dynamic response range) at higher contrasts than nonlagged X cells. These results indicated that nonlagged cells are well suited for detection of small contrasts, whereas lagged cells may discriminate between contrasts over a larger range. The contrast gain and the contrast corresponding to the midpoint of the dynamic response range were similar for X and Y cells. The latency to onset and to half-rise of the visual response decreased with increasing contrast, most pronounced for lagged cells. Even at the highest contrasts, the latency of lagged cells remained longer than for nonlagged cells. For many lagged cells, the latency to half-fall decreased with increasing contrast. It is shown that the differences in the response vs. contrast characteristics between lagged and nonlagged X cells in the cat are similar to the differences between the parvocellular and magnocellular neurones in the monkey.

Contrast sensitivity is a useful measure of the ability of an observer to distinguish contrast signals from noise. Although usually applied to human observers, contrast sensitivity can also be defined operationally for individual visual neurons. In a model linear neuron consisting of a filter and noise source, this operational measure is a function of filter gain, noise power spectrum, signal duration, and a performance criterion. This definition allows one to relate the sensitivities of linear neurons at different levels in the visual pathway. Mathematical formulae describing these relationships are derived, and the general model is applied to the specific problem of relating the sensitivities of parvocellular LGN neurons and cortical simple cells in the primate.

We examined the laminar distribution of corticogeniculate neurons in the macaque striate cortex labeled by axonal transport following injections of retrograde tracers into the lateral geniculate nucleus (LGN). Large injections of retrograde tracers involving all layers of the LGN resulted in a distinctive bilaminar distribution of labeled cells in cortical layer 6. One tier of labeled neurons was located along the layer 5–6 border and a second was located near the bottom of the layer, leaving the middle of layer 6 largely free of labeled neurons. Following injections of tracers that were restricted to the magnocellular layers of the LGN, almost all of the labeled neurons were located in the lower tier. In contrast, following injections of retrograde tracers confined to the parvocellular layers of the LGN, labeled cells were found in both tiers, with the greatest number in the upper tier. Thus, layer 6 of macaque striate cortex consists of three distinct sublayers only two of which are the source of descending projections to the LGN: an upper tier that projects exclusively to the parvocellular layers and a lower tier that projects to both magnocellular and parvocellular layers.