Golgi type II interneurons in the neuronal circuit of the monkey lateral geniculate nucleus

Summary Total excision of areas 17-18-19 in the monkey leads to disappearance of relay cells and corticogeniculate axon terminals in the LGN (lateral geniculate nucleus). The few remaining neurons can be safely considered as Golgi type II cells. Electron microscopic examination of such material revealed small ovoid neurons and synaptic clusters encapsulated by glia. Within the cluster there were the characteristic axon terminal of retinal origin, and a peculiar light and large profile with features of both axons (small, flattened synaptic vesicles) and dendrites (many microtubules, endoplasmic cisterns and free ribosomes) in varying proportions. These elements were also present within the heavily gliotic general neuropil and, in longitudinal section, showed segments with strongly dendritic features, and others with vesicles either scattered or grouped near synaptic specializations. Similar profiles were also seen in normal LGN. Light microscopic examination of Golgi series from adult normal monkeys revealed two types of interneurons in the LGN, both having extremely thin axons which could not correspond in size to the ambiguous profiles described above. The latter could well match the appendages so frequently shown by the dendrites of one of the interneuron types. These findings suggest that the synapses in the glomeruli of LGN previously defined as axo-axonic may in fact be between optic axon terminals and the dendritic profiles with synaptic vesicles delineated in this study. Thence, the role of the Golgi type II interneuron could be interpreted at least in part as lateral inhibition.This research was supported in part by U.S.P.H.S. Grants MH-02261 and K3-EY-16, 865. The technical assistance of Mr. David Kahn and Miss Rosemary Lang is gratefully acknowledged.     

Morphology of identified relay cells and interneurons in the dorsal lateral geniculate nucleus of the rat

Summary The morphology of neurons in the lateral geniculate nucleus of the rat has been examined in both Golgi impregnated and in horseradish peroxidase (HRP) filled material. Two major classes of neurons are seen in Golgi material which encompass the variety of cells described in previous reports. Cells of one group (class A) are routinely labelled by injections of HRP into the visual cortex or optic radiations. This group also displays some morphological variation which may be related to the presence of parallel information channels in the retino-fugal pathway, but clear subgroups cannot be identified on the basis of morphological criteria alone. Cells of the other group (class B) are not labelled by HRP injections into visual cortex or the optic radiations, and are probably local circuit interneurons.     

Serotonin-immunoreactivity in the monkey lateral geniculate nucleus

Summary Serotonin-immunoreactivity in the monkey lateral geniculate nucleus appears as a plexus of fine, beaded fibers decreasing in density from magnocellular to parvocellular laminae. Ultrastructurally, these fibers show strictures and dilations, and are filled with dense round particles as well as granular material attached to outer mitochondrial membranes and microtubules. Most of the profiles followed in serial sections lack morphologically defined synapses. The few synapses observed are asymmetric, some with subjunctional dense bodies. This appearance suggests a possible excitatory effect mainly on interneurons which in turn would inhibit principal cells. Serotonin released non-synaptically may block the delivery of transmitters from retinal terminals and/or the receptors for such transmitters, thereby exerting a modulatory depressing action on principal cells.     

Evidence for two types of GABA-containing interneurons in the A-laminae of the cat lateral geniculate nucleus: a double-label HRP and GABA-immunocytochemical study

Summary Neurons containing GABA immunoreactivity were analyzed in the A-laminae of normal cat LGN and of LGN retrogradely labeled with HRP from the visual cortex. In contrast to retrograde labeling of relay cells, GABA+ cells were devoid of HRP label, providing additional evidence for the interneuronal nature of GABAergic cells in the cat LGN. Cell body area measurements showed that the population of GABA+ cells is composed of a large proportion of small () cells and a smaller proportion of medium size (a) cells. The proportion of GABA+ cells increases from medial to lateral parts of the A-laminae, resembling a similar medio-lateral increase of physiologically defined Y cells and of morphologically defined type 1 cells in these laminae. This suggests that the and GABAergic cells are related to the Y and X geniculo-cortical relay cells, respectively.Supported by grants EY 02877 and HD 03352 from the National Institutes of Health     

Identification of X versus Y properties for interneurons in the A-laminae of the cat's lateral geniculate nucleus

Summary Roughly 25% of the neurons in the A-laminae of the cat's lateral geniculate nucleus are local interneurons, while the remaining 75% are relay cells that project to the visual cortex. The interneurons form the focus of our study. The relay cells are either X or Y cells and are thereby integral links in the parallel and independent retino-geniculo-cortical X and Y pathways. Little is known about the response properties of interneurons, largely because it is difficult to identify them clearly during electrophysiological recording. However, they can be identified by morphological criteria. We thus studied their response properties by recording intracellularly from geniculate neurons to characterize them and then injecting them with horseradish peroxidase (HRP); the HRP labeling subsequently allowed us to distinguish relay cells from interneurons. In this manner, we studied 171 relay cells (83 X and 88 Y) and 15 interneurons. The response properties tested for each of the interneurons were indistinguishable from those of the relay X cells. We conclude that these interneurons are directly innervated by retinogeniculate X axons and are firmly embedded in the X pathway. We found no evidence for inter-neurons in the Y pathway.     

Synaptic organization of the dorsal lateral geniculate nucleus in the adult hamster

Summary The synaptic organization of the sector of the dorsal lateral geniculate nucleus has been examined by electron microscopy in normal adult hamsters and in adult hamsters subjected to unilateral eye enucleation or intravitreal injection of horseradish peroxidase.Two types of neuropil are apparent. Islands of complex neuropil partially enclosed by astrocyte processes (synaptic glomeruli) are surrounded by a sea of simpler non-glomerular neuropil. The latter is dominated by small axon terminals with spherical synaptic vesicles and Gray type 1 axodendritic contacts (SR-boutons) and also contains axon terminals with flattened synaptic vesicles (F-boutons). The glomerular neuropil contains (i) exclusively postsynaptic dendrites and dendritic protrusions of presumptive projection cells; (ii) pre- and postsynaptic pleomorphic-vesiclecontaining P-boutons (interpreted as appendages of the dendrites of interneurons); (iii) large axon terminals containing spherical synaptic vesicles and large pale mitochondria (R-boutons) which were experimentally identified as retinal terminals and which are presynaptic to both projection cell dendrites and P-boutons at Gray type 1 contacts; (iv) F-boutons (minority component). F-boutons and P-boutons are presynaptic to both projection cell dendrites and P-boutons and P-boutons are the intermediate elements of various serial synapses including triplet (triadic) synapses. Medium-large terminals with spherical synatpic vesicles and dark mitochondria (RLD-boutons) which were commonly invaginated by dendritic spines of projection cells in small glomerulus-like formations were also identified. The origin of RLD-boutons is unknown but SR-boutons probably derive chiefly from ipsilateral visual cortex and possibly also from superior colliculus, and non-glomerular F-boutons probably originate in the ipsilateral thalamic reticular nucleus.No differences in synaptic organization were found between the part of the nucleus which receives uncrossed retinal input and the part which receives crossed input, nor were differences seen in the size, fine structure or relationships between the terminals of identified crossed and uncrossed retinal axons.     

Photoreceptor inputs to cat lateral geniculate nucleus cells

Summary The spectral sensitivities of single on- and off-centre, brisk sustained and brisk transient cells recorded from the A laminae of the lateral geniculate nucleus (LGNd) in cats anaesthetised with nitrous oxide and oxygen supplemented with halothane were measured under photopic and mesopic achromatic adapting conditions. All cells possessed spectral sensitivity functions with a single peak at about 556 nm under photopic conditions. Intense chromatic adapting fields superimposed on the photopic background affected neither the shape of the spectral sensitivity functions nor the position of the peak wavelength. Under mesopic adapting conditions cells possessed spectral sensitivities with two peaks, one at 507 nm and one at 556 nm. These results are interpreted as suggesting that the cells of the A laminae of the LGNd receive inputs from rods with maximum sensitivity at 507 nm and a single class of cones maximally sensitive at 556 nm.     

Orientation of dendrites in the lateral geniculate nucleus of the monkey

Summary Quantitative analysis of dendritic orientation in rapid Golgi sections of the lateral geniculate nucleus of Old World monkeys was performed with the help of a computer-microscope and a tree-analysing program. The orientation of intermediate and terminal dendritic segments of parvocellular and magnocellular multipolar neurons was measured at different ages in relationship to a reference line defined by the major direction of afferent fibres visualized in Golgi preparations and by silver staining. The direction of fibre bundles crossing the nucleus is approximately perpendicular to the layers near their apex, but more oblique laterally and medially. There is a clear tendency for terminal dendritic segments of both parvocellular and magnocellular neurons to be oriented preferentially along these fibres and fewer are perpendicular to them. The orientation of intermediate segments is much less clear, showing a more random orientation with regard to the fibres. There is no obvious influence of the order of branching or of the age of the animal (between late gestation and maturity) on the orientation of terminal and intermediate dendritic segments. A parallel study (Leuba and Garey 1984) suggests that there is greater plasticity in the terminal part of the dendritic tree, and it is possible that the maturation of afferent fibres causes these terminal segments to orient along them very early during normal development.     

Morphology of neurons in the lateral geniculate nucleus of the monkey

Summary Rapid Golgi preparations of the lateral geniculate nucleus of old- and new-world monkeys were analysed in an attempt to classify the neuronal types. Four main types are described. The commonest, the multipolar neurons, are found in all laminae. Their somata can be large, medium or small and bear dendrites with sparse spines. Some have a radiate dendritic arbor and others have dendrites grouped in tufts. The next most frequent class is of bipolar neurons with two thick dendrites arising from opposite poles of the soma, which is usually large. Otherwise the dendrites are similar to those of multipolar neurons. Relatively rare is a class of medium-sized neurons with beaded dendrites, found here only in magnocellular laminae. There is a fourth class of small neurons distinguished by fine axonlike dendritic processes. They are in all laminae and form two subgroups, one with very long, cylindrical dendrites and few axon-like processes, the other with shorter dendritic arbors and many axon-like processes. In addition, a class of capsular neurons is found in the circumgeniculate capsule between layer 6 and the pregeniculate nucleus. They are large neurons with umbrella-like dendritic arbors sending ramifications into layer 6. The interlaminar zones contain scattered somata of all types except beaded and capsular neurons.The work described in this paper forms part of a study for a doctoral dissertation in the University of Lausanne by K.D. Saini     

The topographic relationship between shifting binocular maps in the developing dorsal lateral geniculate nucleus

Summary The major mammalian subcortical visual structures receive topographically ordered projections from both eyes. In the adult dorsal lateral geniculate nucleus (dLGN) each projection terminates in separate restricted regions of the nucleus. This pattern is different during development. Initially in ferrets the projections from each eye to the dLGN overlap throughout this structure. Although the projections do not occupy regions that are appropriate given the adult pattern, they are both retinotopically organised. Consequently, the formation of the adult pattern requires that the two retinotopic projections shift in relation to one another. The experiments undertaken here on the newborn ferret demonstrate the relationship between the two unsegregated projections in terms of their retinal origin and relative pattern of projection to the dLGN. By establishing the relationship between the projections at this stage of development it is possible to determine the relative changes that must be made between them in order to bring about the adult pattern of registration. By mapping the two unsegregated projections with a combination of retinal lesions and anterograde tracing methods it is demonstrated that at birth the ipsilateral projection arises from the temporal retina, and the contralateral projection arises from the entire retina. Because of the significant contralateral projection from the temporal retina the relatively sharp nasotemporal division found in the adult is not present at this stage. This element of the contralateral projection maps in continuity with the rest of this projection and terminates at the caudal pole of the nucleus. However, it is probably lost before the adult pattern has clearly started to develop. It is proposed that the representation of the naso-temporal division at the caudal pole of the dLGN is the starting point for the development of the adult pattern of registration. Once this point of registration has been established each map shifts in relation to the other and to the borders of the nucleus to bring about the adult pattern.     

Lateral excitation in the cat lateral geniculate nucleus

Summary Visual responses were elicited by global phase reversal stimuli in cells of the cat dorsal lateral geniculate nucleus (dLGN) after small retinal lesions had been centered on each receptive field. After acute lesions of different sizes exclusively lateral inhibition was found. When GABAergic inhibition was blocked by continuous microiontophoretic application of bicuculline lateral excitation emerged in dLGN cells partially deafferented by small and medium size acute retinal lesions, but not in those affected by large lesions. This indicates the presence of excitatory retinal inputs at the periphery of the dLGN cell dendrites which are normally suppressed by strong, long-ranging lateral inhibitory processes. After chronic deafferentation, the remaining excitatory inputs increase in effectiveness and lateral excitation is seen without blockade of inhibition. The maximal lateral spread of excitation (300 m) in the dLGN is distinctly smaller than the extent of lateral inhibition (1000 m).     

Synaptic reorganization in the lateral geniculate nucleus of the adult cat following chronic decortication

Summary The corona radiata containing all geniculo-cortical and cortico-geniculate fibers was transected in adult cats. One year after the operation synaptic architecture of laminae A and A₁ of the decorticated LGN was investigated utilizing electron-microscopy and Golgi-EM.It was found that synaptic glomeruli became embedded in heavily gliotic neuropile, which contained the dendrites of surviving relay cells in addition to retinal axons and interneuronal processes. In contrast to the intact LGN, where the relay cell dendrites are exclusively postsynaptic, many morphologically identified relay neuronal dendrites of the decorticated LGN also contained large, round synaptic vesicles associated with distinct presynaptic sites. In 60% of all glomeruli, the large presynaptic dendrites of relay neurons occupied a central position and were postsynaptic to retinal axons and interneuronal dendrites/axons, but were presynaptic to other relay dendrites or interneuronal dendritic profiles. Occasional dendro-dendritic synapses between relay cell processes could be observed in the extraglomerular neuropile. Relay cell presynaptic dendrites formed unequivocal Gray I-type synapses, in accordance with the supposed excitatory character of relay cell output.Since sprouting of extrinsic or intrinsic axons could not be observed after decortication, it is proposed that the partial synaptic reorganization of the LGN was primarily due to the compensatory axonization of relay cell dendrites.It is further suggested that the electrophysiologically demonstrated expansion of retinal receptive fields in the chronically decorticated LGN was accomplished by the formation of dendro-dendritic synapses between relay cells and interneurons.     

Binocular interaction in the dorsal lateral geniculate nucleus of the cat

Summary We have investigated binocular interaction in the dorsal lateral geniculate nucleus (LGN) of the cat. Neurons were recorded extracellularly during visual stimulation with sinusoidal gratings which were presented at different interocular phases (disparities). The large majority of cells (91%) exhibited some type of binocular interaction. For 75% and 16% of the total number of cells, the binocular interaction was inhibitory or facilitatory, respectively. For the remaining 9% of cells, no interaction was evident. In marked distinction from visual cortex, the facilitatory and inhibitory interactions in the LGN are independent of the relative interocular phase of the patterns. Neurons in the LGN are therefore insensitive to the stereoscopic depth cue, retinal disparity.     

Dark adaptation and receptive field organisation of cells in the cat lateral geniculate nucleus

Summary The receptive fields of LGN cells were investigated with stationary light and dark spot and annulus stimuli. Stimulus size and background intensity were varied while stimulus/background contrast was kept constant.The speed of dark adaptation varied considerably from cell to cell. Dark adaptation made responses more sustained in all neurones and eliminated the oscillatory on-responses evoked under some conditions in the light-adapted cells. Dark adaptation led also to a disappearance of early phasic inhibition in on-responses, and increased response rise time and latency.The power of surround responses to inhibit centre responses decreased slightly at low levels of light adaptation in LGN cells but much less than in retinal ganglion cells. Some other traces of changing retinal surround effects also appeared in the LGN on dark adaptation. For example, the functional size of receptive fields increased at low levels of illuminance as has been observed in retinal ganglion cells and the receptive fields as estimated from response peaks were larger than those estimated from sustained components.Trainee of the European Training Programme in Brain and Behaviour Research, 1975.     

Synaptogenesis in the dorsal lateral geniculate nucleus of the rat

Summary Synapse formation and maturation were examined in the rat dorsal lateral geniculate nucleus (dLGN) from birth to adulthood. Examination of animals, whose ages were closely spaced in time, showed that the maturation of the synaptic organization of the nucleus takes place chiefly during the first 3 weeks of postnatal life. This period of maturation may be divided into 3 broad stages. During the first stage, which spans the first 4 days of life, there are only a few immature synapses scattered throughout the nucleus; occasionally aggregates of 3 or 4 synapses are encountered. Dendrodendritic synapses first appear at the end of this stage. The second stage, which lasts from the end of the first stage through day 8, is characterized by intensive synaptogenesis as well as extensive growth and degeneration. For the first time, large boutons resembling retinal terminals form multiple synaptic contacts with dendrites and dendritic protrusions; these synaptic arrangements are partially covered by glial processes.A feature characteristic of the developing dLGN during the first 2 postnatal weeks, and particularly during the second stage, is the presence of membrane specializations that resemble vacant postsynaptic densities. These specializations, which may be unapposed or opposite another neuronal process, decrease in frequency as the number of synapses increases. It is not known whether these densities are converted to synapses or whether they result from loss of presynaptic elements.The third stage in the process of synaptogenesis, which spans a period between days 10 and 20, is characterized by myelination and by the diminution of growth cones, degenerating profiles and vacant postsynaptic densities. There is also a very significant increase in the number and maturation of synapses including synaptic glomeruli. However, it is not until the end of this stage that synapses appear qualitatively indistinguishable from synaptic arrangements identified in adult animals.     

Evidence of a collicular input to the dorsal lateral geniculate nucleus in rabbits — electrophysiology

Summary In anesthetized and paralyzed rabbits, unit responses of lateral geniculate nucleus (LGN) cells to focal electrical stimulation of the superior colliculus were studied. Geniculate responses to collicular stimulation (SCS) were compared with responses to optic nerve shock (ONS). A weak correlation coefficient suggested that collicular stimulation did not fire geniculate cells through collateral activation. Further differentiation between collicular and retinofugal inputs to LGN was made possible by repetitive stimulation. Geniculate cells which responded to collicular stimulation were relay cells as they were antidromically invaded from the visual cortex. This ruled out recordings from the ventral geniculate, since this area does not project to the visual cortex. A direct colliculo-geniculate pathway was revealed by antidromic activation of collicular cells by stimulation of the dorsal LGN. Finally, triggering flashes by collicular firing resulted in a marked modification of the geniculate test response. The results suggest that the superior colliculus sends fibers to the LGN and is capable of modulating the retino-cortical neuronal message at the level of the LGN.     

Postnatal growth of the dorsal lateral geniculate nucleus of the cat

Summary The postnatal growth of the dorsal part of the lateral geniculate nucleus (LGNd) is studied in paraffin sections through the brains of 32 cats of known age. The changes in shape and position of the LGNd are described and it is shown that its volume increases from about 3.4 mm³ at birth to about 26.4 mm³ in the adult cat. When this value is corrected for shrinkage, the volume of the LGNd in the adult cat turns out to be about 44 mm³. The detailed measurements reveal that during the second and third week of postnatal life there is a particularly steep increase in volume and that the final values are already reached at around the 40th day. Concomitant with the increase in volume there is a decrease of the number of cells per unit volume of grey matter. In the binocular segment of lamina A the number of cells decreases from about 470 per (0.1 mm)³ at birth to between 95 and 130 per (0.1 mm)³ in the adult cat. Separate measurements of nerve cells and neuroglial cells indicate that the absolute number of nerve cells remains fairly constant during postnatal life, whereas between the second and sixth week a great number of neuroglial cells are newly formed.Dedicated to Professor W. Bargmann, Kiel, on the occasion of his seventieth birthday     

Interaction between inhibitory pathways to principal cells in the lateral geniculate nucleus of the cat

Summary Inhibitory interactions between interneurones of the lateral geniculate nucleus (LGN) of the cat were studied with an indirect method based on intracellular recordings of synaptic responses in principal cells. Recurrent inhibitory postsynaptic potentials (IPSPs), evoked by antidromic activation of principal cell axons in the visual cortex, were depresse by a preceding stimulation of the optic tract or the visual cortex. Disynaptic feed-forward IPSPs, evoked by optic tract stimulation, were likewise depressed after cortex stimulation. The duration of the depression was in both cases about 100 ms. The effect was not due to conductance changes in the recorded principal cells or to activation of corticogeniculate fibres. The observations indicate that perigeniculate neurones, the recurrent inhibitory interneurones of the LGN, have mutual inhibitory connexions and that they also project to intrageniculate interneurones, the inhibitory cells in the feed-forward pathway to principal cells. These conclusions were supported by intracellular recordings from a few interneurones. No evidence was found for interaction between feed-forward interneurones activated from separate eyes or for a projection from intrageniculate interneurones to perigeniculate cells. The results point to an unexpected similarity in the organization of the recurrent inhibitory system of principal cells in the LGN and of spinal motoneurones. It is suggested that the recurrent system of the LGN serves as a variable gain regulator in analogy with a recently proposed model for the spinal system.     

Spike trains and signaling modes of neurons in the ferret lateral geniculate nucleus

Intracellular recordings were used to examine the action potential firing modes of cells in the ferret lateral geniculate nucleus (LGN) in vitro. We compared the effects of altered membrane voltage on patterns of action potential trains evoked by direct current injection and by retinal afferent (synaptic) stimulation. The results confirm that LGN cells in the ferret can fire action potentials in the burst and tonic modes that have been described previously for other species. At depolarized membrane potentials, LGN neurons respond to sustained depolarization with short-latency trains of action potentials whose frequency is directly proportional to the amount of current injected. At hyperpolarized membrane potentials, LGN cells enter burst mode, in which depolarizing inputs are differentiated into brief high-frequency discharges whose latency varies with membrane potential. We also observed a mixed mode, in which LGN cell responses to synaptic or injected currents within a narrow range of membrane potentials reflect aspects of both burst and tonic firing simultaneously. Thus a striking consequence of the interplay among voltage-dependent membrane conductances in thalamic cells is wide variability in length, duration, and latency of spike discharges elicited by identical stimuli. These results also suggest that the concept that LGN cells display only two active response modes must be expanded to include varying amounts of delay and the possibility of mixed discharges.     

Relation of the parabigeminal nucleus to the superior colliculus and dorsal lateral geniculate nucleus in the hooded rat

Summary The retino-recipient layers of the superior colliculus project predominantly to the dorsal and ventral divisions of the ipsilateral parabigeminal nucleus, while receiving an input chiefly from the medial division of the contralateral nucleus. A variety of retrograde tracing techniques was used to confirm that there is a projection from the medial division of the parabigeminal nucleus to the contralateral dorsal lateral geniculate nucleus in normal adult hooded rats. Some parabigeminal cells branch to supply both dorsal lateral geniculate nucleus and retino-recipient layers of the superior colliculus.