Neuronal and synaptic organization of the lateral geniculate nucleus of the tree shrew,Tupaia glis

Summary The ultrastructural study of the lateral geniculate nucleus (LGN) of the tree shrew (Tupaia glis) revealed two types of neurons: (1) a large thalamocortical relay cell (TCR), which may bear cilia, and (2) a small Golgi type-II interneuron (IN) with an invaginated nucleus. The narrow rim of pale cytoplasm of the IN contains fewer lysosomes and fewer Nissl bodies than the cytoplasm of the TCR. The IN perikarya, which in some cases establish somatosomatic contacts, frequently contain flattened or pleomorphic synaptic vesicles. The ratio of TCR to IN is 31.Three types of axon terminals were observed in the LGN. Two of them contain round synaptic vesicles but differ in size. The large RL boutons undergo dark degeneration after enucleation; they are the terminals of retino-geniculate fibers. The smaller RS boutons show dark degeneration after ablation of the visual cortex; they are the terminals of the cortico-geniculate fibers. The third type of bouton (F₁ does not degenerate after either intervention. The boutons of this type are filled with flattened vesicles and are believed to be intrageniculate terminals. F₂-profiles were interpreted as presynaptic dendrites of the IN. The characteristic synaptic glomeruli found in the LGN contain in their center an optic terminal. These optic terminals establish synaptic contacts with dendrites or spine-like dendritic protrusions of TCRs as well as with presynaptic dendrites. Synaptic triads were also seen. The distribution of the individual types of synaptic contacts in layers 3 and 4 was determined. Layer 4 contains only one third of the retino-geniculate synapses and of the synaptic contacts of F₁-terminals.     

A retinal projection to the lateral hypothalamus in the rat

Summary This study presents evidence for a retinal projection to neurons in the lateral hypothalamic area (LHA) of the albino rat. In Golgi-Kopsch material dendrites from LHA-neurons are observed to extend through the supraoptic commissures into the optic tract. The presence of dendrites in the optic tract is confirmed by electron microscopy. Numerous axon terminals are observed forming asymmetric synaptic contacts with these dendritic profiles. Following bilateral enucleation, many of the preterminal axons and terminals in synaptic contact with dendrites in the optic tract demonstrate dark degeneration. After intraocular injection of horseradish peroxidase, there is marked labeling of preterminal axons and terminals in the optic tract. These observations indicate that LHA neurons receive a direct retinal projection from terminals making synaptic contact with dendrites of LHA-neurons extending into the optic tract.     

Axonal transport of actin in rabbit retinal ganglion cells

We labeled proteins in the cell bodies of rabbit retinal ganglion cells with [35S]methionine and subsequently observed the appearance of radioactive actin in tissues containing the axons and synaptic terminals of these neurons, i.e., the optic nerve (ON), optic tract (OT), lateral geniculate nucleus (LGN) and the superior colliculus (SC). The temporal sequence of appearance of labeled actin (which was identified by its specific binding to DNase I, its electrophoretic mobility, and its peptide map) in these tissues indicated that actin is an axonally transported protein with a maximum transport velocity of 3.4--4.3 mm/d. The kinetics of labeling actin were similar to the kinetics of labeling two proteins (M1 and M2) which resemble myosin; these myosin-like proteins were previously found to be included in the groups of proteins (groups III and IV) transported with the third and fourth most rapid maximum velocities. The similarity in transport between actin and myosin-like proteins supports the idea that a number of proteins in the third and fourth transport groups may be functionally related by virtue of their involvement in a force-generating mechanism and suggests the possibility that these proteins may be axonally transported as a preformed force-generating unit.     

Degeneration in the parvocellular portion of the lateral geniculate nucleus of the cebus monkey

Summary The synaptology of the Cebus lateral geniculate nucleus (LGN) was studied after varying (3–15 days) periods of survival following unilateral and bilateral eye enucleations. Part of the material was processed with the Glees and Nauta techniques for light microscopy while the rest was processed for electron microscope observation. The study revealed a variety of degenerated terminals in the parvocellular portion of the LGN and allowed the differentiation of the retinal from the extraretinal terminals. The most frequent synaptic type of retinal origin is a glomerular large central terminal (up to 20 long) which makes axodendritic and axoaxonic synaptic contacts with geniculate dendrites and peripheral small terminals. Simple axodendritic and axosomatic terminals of retinal and extraretinal origin were also found. The early changes affecting the geniculate neurons and astrocytes during the degenerative process are described.These results are discussed in relation to: 1) previous work on the LGN synaptology of cats and macaques; 2) the physiology of the LGN; 3) the phagocytic role of astrocytes; 4) the general problem of degeneration in the central nervous system. In addition, a correlation between the light and electron microscope observations is attempted.Work supported by Grants from the National Council to Combat Blindness, Inc. N.Y., U.S.A. (Fight for Sight Grant-in-Aid-G-340), the AF-AFOSR Grant No. 963/67-68, and the Consejo Nacional de Investigaciones Cientificas y Técnicas, Buenos Aires, Argentina.The authors acknowledge the continuous advice and encouragement received from Prof. E. de Robertis throughout all the phases of the project. The expert technical assistance of Miss E. di Matteo, Mr. A. Sáenz and Mr. R. Castelli is also gratefully acknowledged.     

Parvalbumin,calbindin, and calretinin mark distinct pathways during development of monkey dorsal lateral geniculate nucleus

Immunocyochemical labeling was applied to follow the developmental changes in the calcium-binding proteins parvalbumin (PV), calbindin D28k (CaB), and calretinin (CaR) during fetal and infant development of Macaca monkey dorsal lateral geniculate nucleus (LGN). For all three proteins, LGN cell body and retinal ganglion cell (RGC) axon labeling patterns changed temporally and spatially over development, and many of these were LGN laminar specific. CaR+ and CaB+ cells were present at the youngest age studied, fetal day 55 (F55). After lamination of the LGN occurred between F90 and F115, CaR+ and CaB+ neurons were specific markers for the S, intercalated, and interlaminar layers. Double label immunocytochemistry showed that all CaR+ cells contained CaB, and none contained GABA. CaR+ cell bodies decreased in number soon after birth so that adult LGN contained only a very small number of CaR+ cells. These patterns and cell counts indicated that a downregulation of CaR had occurred in the CaB+ population. Although CaB+ cell density in S and interlaminar zones declined in the adult, cell counts indicated that this is due to dilution of a stable population into a much larger nucleus during development. PV+ cells appeared at F85 only within the putative magnocellular (M) and parvocellular (P) layers, and PV remained a marker for these layers throughout development. Fetal PV cells also contained GABA, indicating that they were LGN interneurons. After birth, GABA−/PV+ cell numbers increased dramatically throughout the whole nucleus so that by the end of the first year, P and M layers were filled with PV+ cells. Their number and size indicated that these were the LGN projection neurons. Beginning at F66, bundles of PV+ axons occupied the anterior-middle LGN and filled the optic tract. Up to F101, PV+ synaptic terminals were restricted to P layers, but after F132 labeling in M layers was heavier than in P layers. Axonal labeling for CaR began at F125. Prenatally CaR+ terminals were present mainly in P layers, whereas by postnatal 9 weeks labeling in M layers much exceeded P layers. Axonal labeling for CaB was present at F132, but CaB+ terminals were observed only after birth with labeling always heavier in M than P layers. By postnatal 9 weeks, PV, CaR, and CaB were colocalized in the same axons and terminals. These experiments indicated that during development and in the adult LGN, both CaR and CaB were markers for the LGN neurons in the S and intercalated pathway. CaR was present transiently while CaB persisted into adulthood. PV was a M and P layer marker first for interneurons and later for projection cells. The complex temporal developmental patterns found in this study suggested that viewing PV, CaB, and CaR simply as calcium-buffering proteins severely underestimates their functional roles during visual system maturation. © 1996 John Wiley & Sons, Inc.     

猫外侧膝状体年龄相关性形态学变化

目的比较青年猫与老年猫外侧膝状体(lateral geniculate nucleus,LGN)神经元及γ-氨基丁酸(gama-aminobutyric acid,GABA)能神经元的年龄相关性变化,探讨老年个体视觉功能衰退的相关神经机理。方法Nissl染色示猫外侧膝状体分层结构(A、A1、C3层)及神经元,免疫组织化学法示GABA免疫阳性神经元。光镜下观察、拍照,Nissl染色切片测量外侧膝状体各层厚度、神经元胞体直径并计数神经元数量;免疫组化染色切片测量外侧膝状体各层中GABA阳性神经元胞体直径并计数GABA阳性神经元数量。结果青年猫及老年猫外侧膝状体各层厚度、神经元数量及胞体直径无明显改变(P>0.05);与青年猫相比,老年猫外侧膝状体各层中GABA阳性神经元数量及胞体直径均有不同程度的显著下降(P<0.01),且GABA免疫阳性反应减弱。结论在动物个体衰老进程中,外侧膝状体总体神经元保持相对稳定可能对老年个体维持视觉功能具有一定意义;老年个体外侧膝状体GABA能神经元对视觉信息传递及整合过程的抑制性调节功能削弱,可能是外侧膝状体水平上导致老年个体视觉功能衰退的原因之一。     

Transneuronal uptake of horseradish peroxidase in the central nervous system of dipterous insects

Summary Horseradish peroxidase (HRP) applied to lesioned neurons in the retina and thoracic ganglia of the flies Musca, Calliphora and Drosophila labeled axon terminals, dendrites and perikarya of the severed neurons after anterograde or retrograde passage. In addition, HRP reaction product secondarily labeled intact neurons that are contiguous with injured nerve cells. In many cases labeling of optic lobe neurons remote from primarily filled ones was also seen (here called tertiary labeling). HRP labeling was extensive and both primarily and transneuronally filled neurons could be resolved in almost as much detail as Golgi-impregnated or cobalt-silver-labeled cells. Electron microscopy showed that in both primarily and secondarily filled neurons, reaction product was distributed diffusely in the cytoplasm.Transneuronal uptake of HRP was specific to certain types of neurons in the brain and thus displayed certain pathways. The pathways resolved by transneuronal labeling with HRP extend from the optic lobes to the thoracic ganglia and include visual neurons previously identified electrophysiologically and anatomically.Transneuronal HRP uptake, although believed to occur in vivo, could not be shown to be dependent on synaptic activity. Three other heme peptides tested were taken up by injured neurons, but showed no transneuronal labeling: lactoperoxidase, cytochrome c, and microperoxidase.     

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.     

Experimental morphological study of endings of propriospinal fibers of the lateral funiculus in the cat cervical spinal cord

The distribution and ultrastructure of terminals of the propriospinal fibers of the lateral funiculus in the cervical segments of the cat spinal cord were studied by the experimental degeneration method. A preliminary lateral hemisection of the spinal cord was carried out 5–6 months earlier at the level of segments C2 or C3 to destroy all the long descending pathways; the lateral funiculus was then divided at the level of C4 or C5. It was shown by the method of Fink and Heimer that terminals of descending and ascending propriospinal pathways damaged by the second division are distributed in the gray matter ipsilaterally in the lateral zones of Rexed's laminase V–VII and also in the dorsolateral motor nuclei. An electron-microscopic study showed that the synapses of the degenerating terminals are mainly axo-dendritic in type and account for 14.5% of the total number of terminals counted. Residual synaptic vesicles in these terminals were spherical in shape. The mean diameter of the degenerating myelinated propriospinal fibers in the lateral funiculus was 10±3 µ. The results of this investigation were compared with those of electrophysiological investigations of the function of propriospinal neurons.     

Propagation of tau pathology in a model of early Alzheimer's disease

Neurofibrillary tangles advance from layer II of the entorhinal cortex (EC-II) toward limbic and association cortices as Alzheimer's disease evolves. However, the mechanism involved in this hierarchical pattern of disease progression is unknown. We describe a transgenic mouse model in which overexpression of human tau P301L is restricted to EC-II. Tau pathology progresses from EC transgene-expressing neurons to neurons without detectable transgene expression, first to EC neighboring cells, followed by propagation to neurons downstream in the synaptic circuit such as the dentate gyrus, CA fields of the hippocampus, and cingulate cortex. Human tau protein spreads to these regions and coaggregates with endogenous mouse tau. With age, synaptic degeneration occurs in the entorhinal target zone and EC neurons are lost. These data suggest that a sequence of progressive misfolding of tau proteins, circuit-based transfer to new cell populations, and deafferentation induced degeneration are part of a process of tau-induced neurodegeneration.     

Transneuronal degeneration in the Rolando substance of the primate spinal cord evoked by axotomy-induced transganglionic degenerative atrophy of central primary sensory terminals

Summary Transection of the sciatic nerve in Rhesus monkeys and the consequent transganglionic degenerative atrophy (TDA) of central terminals of primary afferents result in transneuronal degeneration of substantia gelatinosa (SG) cells. Severe degeneration is characterized by an increased electron density of the nucleus and by conspicuous shrinkage of the cytoplasm, mitochondrial swelling, dilation of cisterns of the rough-surfaced endoplasmic reticulum, accumulation of free ribosomes and an electron-dense material in the cytoplasm. In the mild form, dilation of cisternal elements of the endoplasmic reticulum, swollen mitochondria and accumulation of free ribosomes takes place. About 10% of SG cells in segment L₅ undergo the severe form whereas the rest shows signs of the mild form. Cytoplasmic alterations that occur during transneuronal degeneration seem to start at the level of subsurface cisterns. Dendrites and axons of transneuronally degenerating SG cells also show a conspicuous electron density. By analyzing the synaptic relationships of such darkened dendrites, connections in the upper dorsal horn can be deciphered. Modular units of the primary nociceptive analyzer that evaluate noxious and innocuous inputs on the basis of thin versus thick (AC/A) afferent activity and subjecting them to descending control appear to be recruited from structurally dispersed elements of synaptic glomeruli. These are arranged alongside dendritic processes of large antenna cells which relay impulses to projection cells of the spinothalamic tract.     

Feed-forward synchronization: propagation of temporal patterns along the retinothalamocortical pathway

Visual responses in the cortex and lateral geniculate nucleus (LGN) are often associated with synchronous oscillatory patterning. In this short review, we examine the possible relationships between subcortical and cortical synchronization mechanisms. Our results obtained from simultaneous multi-unit recordings show strong synchronization of oscillatory responses between retina, LGN and cortex, indicating that cortical neurons can be synchronized by oscillatory activity relayed through the LGN. This feed-forward synchronization mechanism operating in the 60 to 120 Hz frequency range was observed mostly for static stimuli. In response to moving stimuli, by contrast, cortical synchronization was independent of oscillatory inputs from the LGN, with oscillation frequency in the range of 30 to 60 Hz. The functional implications of synchronization of activity from parallel channels are discussed, in particular its significance for signal transmission and cortical integration processes.     

A model for predicting masking-period patterns

Information calculations were performed using different codes for the same neuronal impulse data. Under various stimulus conditions the data were obtained from first, second and fourth order neurons (muscle spindles, neurons of the dorsal spino-cerebellar tract and principal cells of the lateral geniculate body of the cat) which had different transneuronal couplings between input and output. A code matched approximately to the signal transfer properties of the investigated neuronal systems was applied. This code was realized by performing a time-weighted average of the input signal with the weighting function being derived from the cross-correlation between the neuronal input and output. Computations of the transinformation using this weighted-average code and the rate code (frequency code) were carried out to show the loss of transinformation due to restrictions in these codes. This loss was determined by comparison with calculations without code restrictions (signal code). In all computations the weighted-average code yielded results ranging from 90 to 99% of those of the signal code. This demonstrates that nearly all information is transmitted by the linear part of the coupling. The results of the rate code did not approximate those of the signal code as closely (5–92%) as in the case of the weighted-average code indicating an unreliability in the rate code when applied to transneuronal signal transmission. Reasons for this unreliability are discussed.     

Invagination of presynaptic ribbons in the fly's optic lobe following loss of their target neuron.

In the first optic neuropile of the housefly Musca, photoreceptor terminals innervate fixed clusters of interneurons, one of which is the monopolar cell L2; L2's synapses in turn feed back upon the terminals. We examined the ultrastructure of these feedback synapses following degeneration of their normal targets, the receptor terminals; this was accomplished by photo-ablating the receptor cells after intraretinal injections of sulforhodamine. Even when all the terminals degenerated, their deafferentated target cells, including L2, remained structurally intact for at least 14 d. Despite this lack of obvious trans-synaptic degeneration, L2's synaptic connections did alter. Presynaptic organelles of the feedback synapses, synaptic ribbons and associated synaptic vesicles, soon appeared in L2's cytoplasm, separating from their site of attachment at the presynaptic membrane by invagination. Similar free-floating organelles and vesicles also occurred in another monopolar cell, L4. They were also occasionally encountered in L2, in normal, newly emerged flies at a time when a naturally occurring loss of feedback synapses is greatest. We interpret the process of internalization that forms these floating ribbons to be the first step in synaptic loss which occurs spontaneously, and that the rate is enhanced in L2 when its main synaptic targets, the receptor terminals, degenerate.     

α-Synuclein accumulation reduces GABAergic inhibitory transmission in a model of multiple system atrophy

Multiple system atrophy is a neurodegenerative disease caused by abnormal α-synuclein (α-syn) accumulation in oligodendrocytes and neurons. We previously demonstrated that transgenic (Tg) mice that selectively overexpressed human α-syn in oligodendrocytes exhibited neuronal α-syn accumulation. Microtubule β-III tubulin binds to endogenous neuronal α-syn to form an insoluble complex, leading to progressive neuronal degeneration. α-Syn accumulation is increased in the presynaptic terminals of Tg mice neurons and may reduce neurotransmitter release. To clarify the mechanisms underlying its involvement in neuronal dysfunction, in the present study, we investigated the effects of neuronal α-syn accumulation on synaptic function in Tg mice. Using whole-cell patch-clamp recording, we found that the frequency of miniature inhibitory postsynaptic currents was reduced in Tg mice. Furthermore, a microtubule depolymerizing agent restored normal frequencies of miniature inhibitory postsynaptic currents in Tg mice. These findings suggest that α-syn and β-III tubulin protein complex plays roles for regulation of synaptic vesicle release in GABAergic interneurons, and it causes to reduce GABAergic inhibitory transmission.     

猫外膝体细胞和视网膜神经节细胞对正弦调制光刺激反应的相位特性

记录了猫外膝体细胞和视交叉纤维对正弦调制光点刺激的反应,作成反应时间直方图(PSTH)。用博里叶分析方法测量不同时间频率下反应的基波相位,作相位-频率特性曲线(PFC)。在暗适应条件下用锥系统的阈下刺激分离出杆系统的反应,这时外膝体细胞的相-频特性为一条负斜率的直线。由斜率所推算的潜伏期平均为81ms。在间视条件下,用 Stiles的二色阈法,分离出锥系统的反应,在这种情况下,相-频特性出现一个十分明显的转折。低频段回归线所对应的潜伏期平均为 107ms,高频段为 39ms。用同样方法分析了神经节细胞(视交叉纤维)的相位-频率特性,结果与外膝体细胞相似,说明与锥系统及杆系统活动有关的时间频率通道在视网膜就已经形成。     

The intrinsic neuronal organisation of the nucleus of the basal optic root in the domestic chicken; a light and electron microscopic study using anterograde tracers and postembedding GABA-immunostaining

The intrinsic neuronal organisation in the nucleus of the basal optic root of chickens was investigated. The divergent connections with various areas and the functional complexity of the nucleus require a complex intrinsic structural arrangement. Therefore, an analysis of Golgi impregnated material, ultrastructure, GABA-immunocytochemistry and biotinylated dextran-amine anterograde tracer analysis of the nucleus was carried out. In the Golgi analysis, a characteristic dendritic ramification pattern of two types of putative projection neurons was observed. These neurons form dendritic nests with their overlapping dendritic terminal sections, that develop synaptic fields with the optic fibre terminals. These synaptic fields were confirmed by electron microscopy. GABA-immunopositive terminals synapse with distinct loci of the dendritic trees of projection neurons; they may therefore play an important role in the inhibitory-modulatory system of the nucleus of the basal optic root. The GABA-immunopositive terminals derive from small and/or elongated local circuit neurons which receive retinal afferents, and from myelinated fibres afferents to the nucleus of unknown origin.     

A Burst-Based “Hebbian” Learning Rule at Retinogeniculate Synapses Links Retinal Waves to Activity-Dependent Refinement

Patterned spontaneous activity in the developing retina is necessary to drive synaptic refinement in the lateral geniculate nucleus (LGN). Using perforated patch recordings from neurons in LGN slices during the period of eye segregation, we examine how such burst-based activity can instruct this refinement. Retinogeniculate synapses have a novel learning rule that depends on the latencies between pre- and postsynaptic bursts on the order of one second: coincident bursts produce long-lasting synaptic enhancement, whereas non-overlapping bursts produce mild synaptic weakening. It is consistent with “Hebbian” development thought to exist at this synapse, and we demonstrate computationally that such a rule can robustly use retinal waves to drive eye segregation and retinotopic refinement. Thus, by measuring plasticity induced by natural activity patterns, synaptic learning rules can be linked directly to their larger role in instructing the patterning of neural connectivity.     

GABA-immunohistological observations, at the electron-microscopical level, of the neurons of isthmic nuclei in chicken, Gallus domesticus

Following a demonstration of Golgi-impregnated neurons and their terminal axon arborization in the optic tectum, the neurons of the nucleus parvocellularis and magnocellularis isthmi were studied by means of postembedded electron-microscopical (EM) γ-aminobutyric acid (GABA)-immunogold staining. In the parvocellular nucleus, none of the neuronal cell bodies or dendrites displayed GABA-like immunoreactivity in EM preparations stained by postembedded GABA-immunogold. However, numerous GABA-like immunoreactive and also unlabeled terminals established synapses with GABA-negative neurons. GABA-like immunoreactive terminals were usually found at the dendritic origin. Around the dendritic profiles, isolated synapses of both GABA-like immunoreactive and immunonegative terminals established glomerulus-like structures enclosed by glial processes. All giant and large neurons of the magnocellular nucleus of the isthmi displayed GABA-like immunoreactivity. Their cell surface was completely covered by GABA-like immunoreactive and unlabeled terminals that established synapses with the neurons. These neurons are thought to send axon collaterals to the parvocellular nucleus; their axons enter the tectum opticum. The morphological characteristics of neurons of both isthmic nuclei are like those of interneurons, because of their numerous axosomatic synapses with both asymmetrical and symmetrical features. These neurons are not located among their target neurons and exert their modulatory effect on optic transmission in the optic tectum at a distance.