Organized arrangement of orientation-sensitive relay cells in the cat's dorsal lateral geniculate nucleus

We studied the physiological orientation biases of over 700 relay cells in the cat's dorsal lateral geniculate nucleus (LGNd). Relay cells were sampled at regular intervals along horizontally as well as vertically oriented electrode penetrations in a fashion analogous to that used previously in studies of visual cortex (Hubel and Wiesel, 1962). The strengths of the orientation biases and the distributions of the preferred orientations were determined for different classes of relay cells, relay cells in different layers of the LGNd, and relay cells subserving different parts of the visual field. We find that, at the population level, LGNd cells exhibit about the same degree of orientation bias as do the retinal ganglion cells providing their inputs (see also Soodak et al., 1987). Also, as in the retina (Levick and Thibos, 1982; Leventhal and Schall, 1983), most LGNd cells tend to prefer stimuli oriented radially, i.e., parallel to the line connecting their receptive fields to the area centralis projection. However, the radial bias in the LGNd is weaker than in the retina. Moreover, there is a relative overrepresentation of cells preferring tangentially oriented stimuli in the LGNd but not in the retina. As a result of the overrepresentation of cells preferring radial and tangential stimuli, the overall distribution of preferred orientations varies in regions of the LGNd subserving different parts of the visual field. Reconstructions of our electrode penetrations provide evidence that, unlike in the retina, cells having similar preferred orientations are clustered in the LGNd. This clustering is apparent for all cell types and in all parts of laminae A and A1. The tendency to cluster according to preferred orientation is evident for cells preferring radially, intermediately, and tangentially oriented stimuli and thus is not simply a reflection of the radial bias evident among retinal ganglion cells at the population level. It is already known that cells having inputs from different eyes, on-center, off-center, X-, Y-, W-type, and color-sensitive ganglion cells are distributed nonrandomly in the LGNd of cats and monkeys (for review, see Rodieck, 1979; Stone et al., 1979; Lennie, 1981; Stone, 1983). The finding that relay cells having similar preferred orientations are also distributed nonrandomly suggests that the initial sorting of virtually all properties segregated in visual cortex may begin in the LGNd.     

Synaptic development of the mouse dorsal lateral geniculate nucleus

The dorsal lateral geniculate nucleus (dLGN) of the mouse has emerged as a model system in the study of thalamic circuit development. However, there is still a lack of information regarding how and when various types of retinal and nonretinal synapses develop. We examined the synaptic organization of the developing mouse dLGN in the common pigmented C57/BL6 strain, by recording the synaptic responses evoked by electrical stimulation of optic tract axons, and by investigating the ultrastructure of identified synapses. At early postnatal ages (<P12), optic tract evoked responses were primarily excitatory. The full complement of inhibitory responses did not emerge until after eye opening (>P14), when optic tract stimulation routinely evoked an excitatory postsynaptic potential/inhibitory postsynaptic potential (EPSP/IPSP) sequence, with the latter having both a GABA_A and GABA_B component. Electrophysiological and ultrastructural observations were consistent. At P7, many synapses were present, but synaptic profiles lacked the ultrastructural features characteristic of the adult dLGN, and little γ‐aminobutyric acid (GABA) could be detected by using immunocytochemical techniques. In contrast, by P14, GABA staining was robust, mature synaptic profiles of retinal and nonretinal origin were easily distinguished, and the size and proportion of synaptic contacts were similar to those of the adult. The emergence of nonretinal synapses coincides with pruning of retinogeniculate connections, and the transition of retinal activity from spontaneous to visually driven. These results indicate that the synaptic architecture of the mouse dLGN is similar to that of other higher mammals, and thus provides further support for its use as a model system for visual system development. J. Comp. Neurol. 518:622–635, 2010. © 2009 Wiley‐Liss, Inc.     

Extrastriate connectivity of the mouse dorsal lateral geniculate thalamic nucleus

The mammalian visual system is one of the most well-studied brain systems. Visual information from the retina is relayed to the dorsal lateral geniculate nucleus of the thalamus (LGd). The LGd then projects topographically to primary visual cortex (VISp) to mediate visual perception. In this view, the VISp is a critical network hub where visual information must traverse LGd–VISp circuits to reach higher order “extrastriate” visual cortices, which surround the VISp on its medial and lateral borders. However, decades of conflicting reports in a variety of mammals support or refute the existence of extrastriate LGd connections that can bypass the VISp. Here, we provide evidence of bidirectional extrastriate connectivity with the mouse LGd. Using small, discrete coinjections of anterograde and retrograde tracers within the thalamus and cortex, our cross-validated approach identified bidirectional connectivity between LGd and extrastriate visual cortices. We find robust reciprocal connectivity of the medial extrastriate regions with LGd neurons distributed along the “ventral strip” border with the intergeniculate leaflet. In contrast, LGd input to lateral extrastriate regions is sparse, but lateral extrastriate regions return stronger descending projections to localized LGd areas. We show further evidence that axons from lateral extrastriate regions can overlap onto medial extrastriate-projecting LGd neurons in the ventral strip, providing a putative subcortical LGd pathway for communication between medial and lateral extrastriate regions. Overall, our findings support the existence of extrastriate LGd circuits and provide novel understanding of LGd organization in rodent visual system.     

Morphological organization of thalamocortical relay cells in the dorsal lateral geniculate nucleus of the North American opossum

The morphology of relay cells in the dorsal lateral geniculate nucleus of the North American opossum was studied by using both Golgi-Cox material and cells stained from retrograde transport of horseradish peroxidase. In general, soma sizes were largest in the part of the nucleus representing the central retina and decreased from the middle third of the nucleus to the anterior to posterior poles. Relay cells labeled with horseradish peroxidase were found to constitute approximately 90% of the dorsal lateral geniculate nucleus cells and have larger soma diameters than most unlabeled cells. From morphometric analysis of several structural characteristics, three classes of relay cells were identified in both Golgi-Cox and horseradish peroxidase material. Type 1 cells, the predominant class, exhibited radially arranged primary dendritic fields, symmetrically organized relative to projection lines. Type 2 cells had relatively few primary dendrites, and complex dendritic fields that were oriented parallel to projection lines. Least numerous were Type 3 cells, which were characterized by relatively sparse dendritic fields oriented perpendicular to projection lines. An additional class of neuron, Type 4 cells, with small somata and sparse dendritic branching, was found only in Golgi-Cox material. Cells with Type 4 dendritic morphology were not found with retrograde horseradish peroxidase labeling and may represent interneurons. The classification of morphologically characterized cells in the opossum dorsal lateral geniculate nucleus was evaluated quantitatively with multivariate discriminant analysis. The classes are compared to physiologically identified Y-, X-, and W-like relay cells in the opossum and to relay cell classes in other species.     

Ventral lateral geniculate nucleus projects to the dorsal lateral geniculate nucleus in the cat

The lamina C3 of the dorsal lateral geniculate nucleus of the cat does not receive retinal projections but instead receives visual information from the small subpopulation of W-type ganglion cells via the upper substratum of the stratum griseum superficiale of the superior colliculus. We herein report a projection from the lateral division of the ventral lateral geniculate nucleus into the lamina C3 of the dorsal lateral geniculate nucleus. As the lateral division receives projections from the contralateral retina and the ipsilateral upper stratum griseum superficiale of the superior colliculus, we suggest that these regions make up a small cell type W-cell neuronal network that provides visual information to layer I of the striate cortex via the lamina C3.     

Effects of bicuculline on direction-sensitive relay cells in the dorsal lateral geniculate nucleus (LGNd) of cats

The direction sensitivity of relay cells in the cat's dorsal lateral geniculate (LGNd) was measured using sinusoidal grating stimuli before and during local bicuculline administration. One hundred and twenty-eight LGNd relay cells were recorded in laminae A and A1, of which 44 relay cells (34%) were found to be sensitive to direction of stimulus movement. The direction-sensitive LGNd relay cells could be differentiated into two subgroups based on different measures of their response amplitude. Type I cells exhibited their direction sensitivity when the fundamental Fourier component (FFC) of the poststimulus time histograms (PSTHs) was used as response measure, but did not show significant direction sensitivity when mean firing rate was used. Type II cells exhibited their direction sensitivity, no matter whether the FFC or mean firing rate was used as the measure. Of 35 cells analyzed, 27 cells remained direction sensitive during bicuculline administration. At the population level, the direction bias of type I cells did not change systematically, while the direction bias of type II cells decreased significantly during bicuculline administration. These results suggest that the direction bias of these two types of relay cells are mediated by different neural mechanisms. The direction bias of type I cells may involve multiple inputs from spatio-temporally separate subunits within retinal ganglion cells receptive fields. The direction bias of type II cells may involve GABAergic neuronal circuits within the LGNd.     

Effects of bicuculline on signal detectability in lateral geniculate nucleus relay cells

The lateral geniculate nucleus conveys the center-surround organized retinal receptive fields to the cortex in a way that does not significantly alter their spatial structure. However, non-retinal influences may change the 'strength' (detectability) of the signal under conditions of anesthesia, arousal and attention. A previous analysis of receiver operating characteristic curves in cat suggests that a reduction in signal detectability occurs in lateral geniculate nucleus (LGN) relay cells in anesthetized animals in comparison to the retinal afferents. In the present study, it was found that antagonism of GABAA receptors with bicuculline (BIC) increased signal detectability in LGN relay cells in the tree shrew (Tupaia belangeri). This change is consistent with the hypothesis that feedforward and/or feedback GABAergic circuits in the LGN differentially affect the retinogeniculate transfer ratio for visually driven activity versus maintained (spontaneous) activity. Under conditions of arousal or attention, signal detectability may be increased by brainstem activation, thus increasing the flow of information in the visual system.     

Serotonergic inhibition of the dorsal lateral geniculate nucleus

Electrophysiological studies were conducted on chloral hydrate-anesthetized rats to determine if the dorsal raphe nucleus (DR) exerts an inhibitory influence upon the dorsal lateral geniculate nucleus (dLGN), and if this inhibition is mediated by the release of serotonin (5-HT). Conditioning stimuli presented to the DR 100-400 ms before an optic tract (OT) shock significantly lowered the amplitude of OT shock-elicited, postsynaptic, field potentials of less than 3 ms latency. Rare, long-latency, field potentials (greater than 5 ms) were diminished in amplitude when preconditioning intervals were less than 15 ms. Six days after intracerebral injection of the 5-HT neurotoxin, 5,7-dihydroxytryptamine (8 micrograms), into the dLGN, significant reductions were observed in 5-HT and 5-hydroxyindole acetic acid in the dLGN. Field potentials recorded on the sixth day in indoleamine-depleted dLGN were significantly less inhibited by DR preconditioning. Intracerebral injections of a control solution neither altered monoamine levels nor the degree of inhibition by DR preconditioning. These data provide further evidence that inhibition of dLGN by DR is mediated by release of 5-HT.     

The identification of relay neurons in the dorsal lateral geniculate nucleus of monkeys using horseradish peroxidase.

Intraaxonal retrograde transport of the protein horseradish peroxidase (HRP) was used to identify relay neurons in the dorsal lateral geniculate nucleus (LGN) of owl (Aotus trivirgatus) and rhesus (Macaca mulatta) monkeys. In both species, from 94.1-98.6% of the neurons within columns extending through both parvocellular and magnocellular layers were labeled following injection of HRP into striate cortex. Labeled neurons were also identified in the thin ventral-most S(0) Layers. Although most of the cells within the thin interlaminar regions in the LGN of both species were labeled following injections of HRP, many unlabeled neurons were identified within the large cell-rich interlaminar region (IL) between the internal parvocellular and internal magnocellular layers in the LGN of the owl monkey, suggesting that IL may be a specialized region containing a large number of intrinsic neurons. Finally, measurement of the cell diameters of neurons within the densely labeled areas in relay layers revealed that labeled and unlabeled neurons could not be distinguished on the basis of cell body size alone and that some of the smallest cells of the LGN project to striate cortex. These findings indicate that nearly all of the neurons of the main relay layers of the LGN in these two primates are relay cells and that the organization of the LGN in primates may differ significantly from that of other mammals with respect to the percentage of interneurons.     

Response properties of cells in the dorsal lateral geniculate nucleus of the albino rat

The response patterns of cells in the dorsal lateral geniculate nucleus of the albino rat were studied in order to examine the functional organization of the lateral geniculate nucleus. Both photic stimulation and electrical stimulation of the optic tract were used to activate single units in the lateral geniculate nuclei. Three different types of response patterns were found for principal cells, while interneurons all had similar response patterns. The first class of principal cells, E-S cells, responded to stimulation with a period of excitation, followed by a period when activity was suppressed. A second class of cells, S cells, responded to photic stimulation with an initial period when activity was suppressed. The final class of cells, E cells, responded with a period of excitation followed by a return to spontaneous rates of firing. The response patterns of E cells suggest that this type of principal neuron does not receive feedback inhibition of the type proposed in previous models of the lateral geniculate nuclei. Based on these and other observations, a new model of the functional organization of the lateral geniculate nuclei is proposed.     

Effects of early monocular eyelid suture upon development of relay cell classes in the cat's lateral geniculate nucleus

Horseradish peroxidase (HRP) was injected into visual cortex of four normal cats and five cats raised with monocular lid suture, and retrograde labelling was assessed in cells of the lateral geniculate nucleus. In all but one of the sutured cats (noted below) focal injections were carefully limited to area 17 or 18 and analysis of labelling focused on laminae A and A1. The effects of deprivation were indistinguishable whether lamina A or A1 was deprived, and in all cases, the nondeprived laminae had labelling essentially identical to that seen in normal cats. After area 17 injections (bilateral in one normal cat and unilateral in 3 deprived cats), roughly 77% of the cells in nondeprived laminae were labelled and they were mostly small to medium in size. Deprived laminae, when compared to nondeprived laminae, had two abnormalities: (1) cells, both labelled and unlabelled, were smaller; and (2) roughly 11% fewer cells (i.e., 66%) were labelled, and this represents a small but statistically significant difference for each cat. After area 18 injections (bilateral in one normal cat plus unilateral in 3 other normal and 3 deprived cats), roughly 15% of the cells in nondeprived laminae were labelled, and they tended to be large in size. Deprived laminae, when compared to nondeprived laminae, had three abnormalities: (1) only 5–6% of the cells were labelled, and these tended to be quite faintly labelled; (2) the volume occupied by labelled cells was small; and (3) both labelled and unlabelled cells were reduced in size. Finally, large bilateral injections were made throughout occipitotemporal cortex in one lid sutured cat in an effort to label completely the terminal zones of cells in the medial interlaminar nucleus (MIN), a division of the lateral geniculate nucleus; this cat also had a prior intraocular injection of tritiated proline to provide through subsequent autoradiography a delineation of deprived and nondeprived portions of MIN. Roughly 78% of the cells in nondeprived portions of MIN were labelled in this cat. In the deprived portions, only about 51% of the cells were labelled, and these tended to be faintly labelled. Also, labelled cells were smaller, and unlabelled cells were larger in deprived than they were in nondeprived portions. Since prior studies have shown that, within the A laminae, X-cells project exclusively to area 17 whereas the Y-cell population projects to areas 17 and 18, these data are taken as further support of the conclusion that geniculate Y-cells are more seriously affected by the early deprivation than are geniculate X-cell. That is, these data are consistent with the suggestion that a similar population of Y-cells in deprived laminae (roughly 10% of the overall cell total) fail to transport HRP from area 17 or area 18 injections. This can be extended to the MIN, which seems to be comprised nearly exclusively of Y-cells. However, these conclusions must be considered tentative, since interpretation of HRP data can be difficult as evidenced by discrepancies in the literature.     

Cortical projections from the dorsal lateral geniculate nucleus of cats

Lesions were placed in the dorsal lateral geniculate nucleus of cats (LGN) and cortical degeneration studied with a modified Nauta method. Besides local degeneration attributable to the electrode track, dense projections to Areas 17 and 18 ipsilateral to the lesion were found. Medium or dense degeneration was found on both banks of the suprasylvian fissure ipsilaterally and light degeneration widely distributed in Area 19 and on the suprasylvian and posterior ectosylvian gyri. In addition to commissural degeneration homotopic to the electrode track, degenerating fibers were found in the visual areas of the opposite hemisphere, suggesting the presence of a crossed geniculo-cortical pathway.     

Effects of bicuculline on receptive field center sensitivity of relay cells in the lateral geniculate nucleus

The lateral geniculate nucleus (LGN) receives input from the retina that is spatially organized into a receptive-field center and surround. It maintains this organization in the signal that it sends to the visual cortex. Previous studies have focused on changes in the receptive-field 'surround' that are generated at the LGN, possibly as a local contrast enhancement mechanism. The present study suggests a role for the LGN in regulating the receptive-field center sensitivity under the control of GABAergic circuitry. Local microiontophoresis of the GABAA receptor antagonist bicuculline increased the contrast sensitivity of LGN relay cells to many spatial frequencies. Difference of Gaussians analysis showed that the increased was due to an increased sensitivity of the receptive-field center. Similar increases in receptive-field center sensitivity may be produced during behavioral arousal by the action of pontine and mesencephalic pathways upon the activity of the LGN GABAergic circuitry.     

Cellular interrelationships during laminar segregation in the dorsal lateral geniculate nucleus

In order to gain insight into the mechanisms involved in the formation of groupings of functionally similar cells in the developing nervous system, we have studied the formation of cell layers in the developing dorsal lateral geniculate nucleus (dLGN). To examine the possibility that a higher affinity or adhesion between cells in individual layers may play a role in laminar segregation, we studied cellular interrelationships in the dLGN of tree shrews before (P0), during (P4 and P7), and just after (P15) laminar segregation has taken place. We compared our observations at these stages of development with similar observations in the adult. In none of the cases do we see evidence of gap junctions either between adjacent neurons or between neurons and processes in the surrounding neuropil. However, we frequently observe the presence of puncta adherentes between adjacent neurons at all stages of development. These profiles are also present between neurons and cellular processes in the neuropil. We also see subsurface cisternae in all of our cases, although these are more pronounced before and during interlaminar space formation. As with the puncta adherentes, these are found both between adjacent neurons as well as between neurons and other elements in the neuropil. We also see some evidence of what appear to be cytoplasmic bridges between adjacent neurons; these are quite rare but appear to be present only before and during laminar segregation. Finally, we frequently see cytoplasmic processes interdigitated between otherwise immediately adjacent cells. These processes also are often found oriented along other portions of the neuronal plasmalemma. Whether these processes are portions of neuronal growth cones or glial processes is impossible to determine at this time. Because of the potential role glial processes may play in the formation and maintenance of laminar cell groupings during layer formation, we have also made a preliminary survey of whether glial cells can be distinguished ultrastructurally at the stages we have studied.     

Genesis of interneurons in the dorsal lateral geniculate nucleus of the cat

Most neurons in the A-laminae of the cat's dorsal lateral geniculate nucleus (LGN) are born between embryonic days 22 and 32. Whereas approximately 78% of these cells are destined to become geniculocortical relay cells, the remaining 22% of LGN neurons do not appear to establish connections with visual cortex, and therefore can be considered interneurons. In the present study we have combined the 3H-thymidine method for labeling dividing neurons with the retrograde horseradish peroxidase (HRP) method for identifying LGN relay cells in order to study specifically the genesis of interneurons in the cat's LGN. Developing LGN interneurons in 12 kittens were labeled with 3H-thymidine by injecting the radioactive label into the allantoic cavity of their pregnant mothers on different embryonic days. Approximately 8-22 weeks after birth LGN relay cells in the A-laminae were labeled retrogradely by injecting large volumes of HRP into visual cortex areas 17 and 18. LGN cells that could not be labeled retrogradely with HRP were considered to be interneurons. Our results show that interneurons are born on each of the embryonic days studied, E24-E30. This period represents approximately the middle two-thirds of the entire period of LGN neurogenesis. Although the birth rate for interneurons is not uniform, there is no indication from our data that interneurons and relay cells in the cat's LGN are born at different times during LGN neurogenesis.