Regulation of Dendritic Filopodial Interactions by ZO-1 and Implications for Dendrite Morphogenesis

Neuronal dendrites dynamically protrude many fine filopodia in the early stages of neuronal development and gradually establish complex structures. The importance of the dendritic filopodia in the formation of axo-dendritic connections is established, but their role in dendrite morphogenesis remains unknown. Using time-lapse imaging of cultured rat hippocampal neurons, we revealed here that many filopodia dynamically protruded from dendrites and transiently interacted with each other to form dendritic filopodia-filopodia contacts in the early stages of neuronal development. The MAGUK family member, Zonula Occludens-1 (ZO-1), which is known to be associated with the nectin and cadherin cell adhesion systems, was concentrated at these dendritic filopodia-filopodia contact sites and also at the tips of free dendritic filopodia. Overexpression of ZO-1 increased the formation of dendritic filopodia and their interactions, and induced abnormal dendrite morphology. Conversely, knockdown of ZO-1 decreased the formation of dendritic filopodia and their interactions, and induced abnormal dendrite morphology which was different from that induced by the overexpression of ZO-1. The components of the nectin and cadherin systems were co-localized with ZO-1 at the dendritic filopodia-filopodia contact sites, but not at the tips of free dendritic filopodia. Overexpression of ZO-1 increased the accumulation of these cell adhesive components at the dendritic filopodia-filopodia contact sites and stabilized their interactions, whereas knockdown of ZO-1 reduced their accumulation at the dendritic filopodia-filopodia contact sites. These results indicate that ZO-1 regulates dendritic filopodial dynamics, which is implicated in dendrite morphogenesis cooperatively with the nectin and cadherin systems in cultured neurons.     

Rac1 and RhoA GTPases have antagonistic functions during N-cadherin-dependent cell-cell contact formation in C2C12 myoblasts

Background information. N‐cadherin, a member of the Ca²⁺‐dependent cell—cell adhesion molecule family, plays an essential role in the induction of the skeletal muscle differentiation programme. However, the molecular mechanisms which govern the formation of N‐cadherin‐dependent cell—cell contacts in myoblasts remain unexplored. Results. In the present study, we show that N‐cadherin‐dependent cell contact formation in myoblasts is defined by two stages. In the first phase, N‐cadherin is highly mobile in the lamellipodia extensions between the contacting cells. The second stage corresponds to the formation of mature N‐cadherin‐dependent cell contacts, characterized by the immobilization of a pool of N‐cadherin which appears to be clustered in the interdigitated membrane structures that are also membrane attachment sites for F‐actin filaments. We also demonstrated that the formation of N‐cadherin‐dependent cell—cell contacts requires a co‐ordinated and sequential activity of Rac1 and RhoA. Rac1 is involved in the first stage and facilitates N‐cadherin‐dependent cell—cell contact formation, but it is not absolutely required. Conversely, RhoA is necessary for N‐cadherin‐dependent cell contact formation, since, via ROCK (Rho‐associated kinase) signalling and myosin 2 activation, it allows the stabilization of N‐cadherin at the cell—cell contact sites. Conclusions. We have shown that Rac1 and RhoA have opposite effects on N‐cadherin‐dependent cell—cell contact formation in C2C12 myoblasts and act sequentially to allow its formation.     

N‐cadherin prodomain cleavage regulates synapse formation in vivo

Cadherins are initially synthesized bearing a prodomain that is thought to limit adhesion during early stages of biosynthesis. Functional cadherins lack this prodomain, raising the intriguing possibility that cells may utilize prodomain cleavage as a means to temporally or spatially regulate adhesion after delivery of cadherin to the cell surface. In support of this idea, immunostaining for the prodomain of zebrafish N‐cadherin revealed enriched labeling at neuronal surfaces at the soma and along axonal processes. To determine whether post‐translational cleavage of the prodomain affects synapse formation, we imaged Rohon‐Beard cells in zebrafish embryos expressing GFP‐tagged wild‐type N‐cadherin (NCAD‐GFP) or a GFP‐tagged N‐cadherin mutant expressing an uncleavable prodomain (PRON‐GFP) rendering it nonadhesive. NCAD‐GFP accumulated at synaptic microdomains in a developmentally regulated manner, and its overexpression transiently accelerated synapse formation. PRON‐GFP was much more diffusely distributed along the axon and its overexpression delayed synapse formation. Our results support the notion that N‐cadherin serves to stabilize pre‐ to postsynaptic contacts early in synapse development and suggests that regulated cleavage of the N‐cadherin prodomain may be a mechanism by which the kinetics of synaptogenesis are regulated. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009     

RhoA/ROCK and Cdc42 regulate cell‐cell contact and N‐cadherin protein level during neurodetermination of P19 embryonal stem cells

RhoGTPases regulate actin‐based signaling cascades and cellular contacts. In neurogenesis, their action modulates cell migration, neuritogenesis, and synaptogenesis. Murine P19 embryonal stem cells differentiate to neurons upon aggregation in the presence of retinoic acid, and we previously showed that RhoA and Cdc42 RhoGTPases are sequentially up‐regulated during neuroinduction, suggesting a role at this very early developmental stage. In this work, incubation of differentiating P19 cells with C3 toxin resulted in decreased aggregate cohesion and cadherin protein level. In contrast, C3 effects were not observed in cells overexpressing recombinant dominant active RhoA. On the other hand, C3 did not affect cadherin in uninduced cells and their postmitotic neuronal derivatives, respectively expressing E‐ and N‐cadherin. RhoA is thus influential on cell aggregation and cadherin expression during a sensitive time window that corresponds to the switch of E‐ to N‐cadherin. Cell treatment with Y27632 inhibitor of Rho‐associated‐kinase ROCK, or advanced overexpression of Cdc42 by gene transfer of a constitutively active form of the protein reproduced C3 effects. RhoA‐antisense RNA also reduced cadherin level and the size of cell aggregates, and increased the generation of fibroblast‐like cells relative to neurons following neuroinduction. Colchicin, a microtubule disrupter, but not cytochalasin B actin poison, importantly decreased cadherin in neurodifferentiating cells. Overall, our results indicate that the RhoA/ROCK pathway regulates cadherin protein level and cell‐cell interactions during neurodetermination, with an impact on the efficiency of the process. The effect on cadherin seems to involve microtubules. The importance of correct timing of RhoA and Cdc42 functional expression in neurogenesis is also raised. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 289–307, 2004     

The cadherin superfamily in neuronal connections and interactions

Neural development and the organization of complex neuronal circuits involve a number of processes that require cell-cell interaction. During these processes, axons choose specific partners for synapse formation and dendrites elaborate arborizations by interacting with other dendrites. The cadherin superfamily is a group of cell surface receptors that is comprised of more than 100 members. The molecular structures and diversity within this family suggest that these molecules regulate the contacts or signalling between neurons in a variety of ways. In this review I discuss the roles of three subfamilies - classic cadherins, Flamingo/CELSRs and protocadherins - in the regulation of neuronal recognition and connectivity.     

GSKIP,an inhibitor of GSK3β, mediates the N‐cadherin/β‐catenin pool in the differentiation of SH‐SY5Y cells

Emerging evidence has shown that GSK3β plays a pivotal role in regulating the specification of axons and dendrites. Our previous study has shown a novel GSK3β interaction protein (GSKIP) able to negatively regulate GSK3β in Wnt signaling pathway. To further characterize how GSKIP functions in neurons, human neuroblastoma SH‐SY5Y cells treated with retinoic acid (RA) to differentiate to neuron‐like cells was used as a model. Overexpression of GSKIP prevents neurite outgrowth in SH‐SY5Y cells. GSKIP may affect GSK3β activity on neurite outgrowth by inhibiting the specific phosphorylation of tau (ser396). GSKIP also increases β‐catenin in the nucleus and raises the level of cyclin D1 to promote cell‐cycle progression in SH‐SY5Y cells. Additionally, overexpression of GSKIP downregulates N‐cadherin expression, resulting in decreased recruitment of β‐catenin. Moreover, depletion of β‐catenin by small interfering RNA, neurite outgrowth is blocked in SH‐SY5Y cells. Altogether, we propose a model to show that GSKIP regulates the functional interplay of the GSK3β/β‐catenin, β‐catenin/cyclin D1, and β‐catenin/N‐cadherin pool during RA signaling in SH‐SY5Y cells. J. Cell. Biochem. 108: 1325–1336, 2009. © 2009 Wiley‐Liss, Inc.     

Synaptic patterns in the dorsal lateral geniculate nucleus of the monkey

Summary Synaptic junctions are found in all parts of the nucleus, being almost as densely distributed between cell laminae as within these laminae.In addition to the six classical cell laminae, two thin intercalated laminae have been found which lie on each side of lamina 1. These laminae contain small neurons embedded in a zone of small neural processes and many axo-axonal synapses occur there.Three types of axon form synapses in all cell laminae and have been called RLP, RSD and F axons. RLP axons have large terminals which contain loosely packed round synaptic vesicles, RSD axons have small terminals which contain closely packed round vesicles and F axons have terminals intermediate in size containing many flattened vesicles.RLP axons are identified as retinogeniculate fibers. Their terminals are confined to the cell laminae, where they form filamentous contacts upon large dendrites and asymmetrical regular synaptic contacts (with a thin postsynaptic opacity) upon large dendrites and F axons. RSD axons terminate within the cellular laminae and also between them. They form asymmetrical regular synaptic contacts on small dendrites and on F axons. F axons, which also occur throughout the nucleus, form symmetrical regular contacts upon all portions of the geniculate neurons and with other F axons. At axo-axonal junctions the F axon is always postsynaptic.Supported by Grant R 01 NB 06662 from the USPHS and by funds of the Neurological Sciences Group of the Medical Research Council of Canada. Most of the observations were made while R. W. Guillery was a visiting professor in the Department of Physiology at the University of Montreal. We thank the Department of Physiology for their support and Mr. K. Watkins, Mrs. E. Langer and Mrs. B. Yelk for their skillful technical assistance.     

Ultrastructural changes in the gracile nucleus of the spontaneously diabetic BB rat.

The present study describes the structural changes in the gracile nucleus of the spontaneously diabetic BB rat. At 3-7 days post-diabetes, axons, axon terminals and dendrites showed electron-dense degeneration. Degenerating axons were characterized by swollen mitochondria, vacuolation, accumulation of glycogen granules, tubulovesicular elements, neurofilaments and dense lamellar bodies. Degenerating axon terminals consisted of an electron-dense cytoplasm containing swollen mitochondria, vacuoles and clustering of synaptic vesicles. These axon terminals made synaptic contacts with cell somata, dendrites and other axon terminals. Degenerating dendrites were postsynaptic to normal as well as degenerating axon terminals. At 1-3 months post-diabetes, degenerating electron-dense axons, axon terminals and dendrites were widely scattered in the neuropil. Macrophages containing degenerating electron-dense debris were also present. At 6 months post-diabetes, the freshly degenerating neuronal elements encountered were similar to those observed at 3-7 days. However, there were more degenerating profiles at 6 months post-diabetes compared to the earlier time intervals. Terminally degenerating axons were vacuolated and their axoplasm appeared amorphous. It is concluded that degenerative changes occur in the gracile nucleus of the spontaneously diabetic BB rat.     

Profiling Murine Tau with 0N, 1N and 2N Isoform-Specific Antibodies in Brain and Peripheral Organs Reveals Distinct Subcellular Localization,with the 1N Isoform Being Enriched in the Nucleus

In the adult murine brain, the microtubule-associated protein tau exists as three major isoforms, which have four microtubule-binding repeats (4R), with either no (0N), one (1N) or two (2N) amino-terminal inserts. The human brain expresses three additional isoforms with three microtubule-binding repeats (3R) each. However, little is known about the role of the amino-terminal inserts and how the 0N, 1N and 2N tau species differ. In order to investigate this, we generated a series of isoform-specific antibodies and performed a profiling by Western blotting and immunohistochemical analyses using wild-type mice in three age groups: two months, two weeks and postnatal day 0 (P0). This revealed that the brain is the only organ to express tau at significant levels, with 0N4R being the predominant isoform in the two month-old adult. Subcellular fractionation of the brain showed that the 1N isoform is over-represented in the soluble nuclear fraction. This is in agreement with the immunohistochemical analysis as the 1N isoform strongly localizes to the neuronal nucleus, although it is also found in cell bodies and dendrites, but not axons. The 0N isoform is mainly found in cell bodies and axons, whereas nuclei and dendrites are only slightly stained with the 0N antibody. The 2N isoform is highly expressed in axons and in cell bodies, with a detectable expression in dendrites and a very slight expression in nuclei. The 2N isoform that was undetectable at P0, in adult brain was mainly found localized to cell bodies and dendrites. Together these findings reveal significant differences between the three murine tau isoforms that are likely to reflect different neuronal functions.     

Unequal competition between axons for neuronal targets.

Precise wiring of the nervous system depends not only on a matching between neurons and their synaptic targets, but also upon competition between neurons for particular targets. Neurons in adult leeches regenerate synaptic connections with their usual neuronal targets in the central nervous system, selecting only those targets with which they connect during embryogenesis. Thus during development axons of nociceptive (N) sensory cells make contacts on the cell bodies of certain neurons in adjacent ganglia but not upon those same types of cells in their own ganglion. After injury the N cell axons accurately regenerate contacts on the appropriate target cells. An abnormal feature observed after injury is that N cell axons sprout and grow to make contacts upon cell bodies within their own ganglion. This is a consequence of the normal innervation of those cells having been removed, thereby eliminating the source of competition. Similar competition during embryogenesis may guide the formation of selective connections.     

Cadherin-mediated regulation of microtubule dynamics

Epithelial polarization and neuronal outgrowth require the assembly of microtubule arrays that are not associated with centrosomes. As these processes generally involve contact interactions mediated by cadherins, we investigated the potential role of cadherin signalling in the stabilization of non-centrosomal microtubules. Here we show that expression of cadherins in centrosome-free cytoplasts increases levels of microtubule polymer and changes the behaviour of microtubules from treadmilling to dynamic instability. This effect is not a result of cadherin expression per se but depends on the formation of cell-cell contacts. The effect of cell-cell contacts is mimicked by application of beads coated with stimulatory anti-cadherin antibody and is suppressed by overexpression of the cytoplasmic cadherin tail. We therefore propose that cadherins initiate a signalling pathway that alters microtubule organization by stabilizing microtubule ends.     

Circadian Control of Dendrite Morphology in the Visual System of Drosophila melanogaster

Background

In the first optic neuropil (lamina) of the fly''s visual system, monopolar cells L1 and L2 and glia show circadian rhythms in morphological plasticity. They change their size and shape during the day and night. The most pronounced changes have been detected in circadian size of the L2 axons. Looking for a functional significance of the circadian plasticity observed in axons, we examined the morphological plasticity of the L2 dendrites. They extend from axons and harbor postsynaptic sites of tetrad synaptic contacts from the photoreceptor terminals.

Methodology/Principal Findings

The plasticity of L2 dendrites was evaluated by measuring an outline of the L2 dendritic trees. These were from confocal images of cross sections of L2 cells labeled with GFP. They were in wild-type and clock mutant flies held under different light conditions and sacrified at different time points. We found that the L2 dendrites are longest at the beginning of the day in both males and females. This rhythm observed under a day/night regime (LD) was maintained in constant darkness (DD) but not in continuous light (LL). This rhythm was not present in the arrhythmic per⁰¹ mutant in LD or in DD. In the clock photoreceptor cry^b mutant the rhythm was maintained but its pattern was different than that observed in wild-type flies.

Conclusions/Significance

The results obtained showed that the L2 dendrites exhibit circadian structural plasticity. Their morphology is controlled by the per gene-dependent circadian clock. The L2 dendrites are longest at the beginning of the day when the daytime tetrad presynaptic sites are most numerous and L2 axons are swollen. The presence of the rhythm, but with a different pattern in cry^b mutants in LD and DD indicates a new role of cry in the visual system. The new role is in maintaining the circadian pattern of changes of the L2 dendrite length and shape.     

RhoA/ROCK and Cdc42 regulate cell-cell contact and N-cadherin protein level during neurodetermination of P19 embryonal stem cells

RhoGTPases regulate actin-based signaling cascades and cellular contacts. In neurogenesis, their action modulates cell migration, neuritogenesis, and synaptogenesis. Murine P19 embryonal stem cells differentiate to neurons upon aggregation in the presence of retinoic acid, and we previously showed that RhoA and Cdc42 RhoGTPases are sequentially up-regulated during neuroinduction, suggesting a role at this very early developmental stage. In this work, incubation of differentiating P19 cells with C3 toxin resulted in decreased aggregate cohesion and cadherin protein level. In contrast, C3 effects were not observed in cells overexpressing recombinant dominant active RhoA. On the other hand, C3 did not affect cadherin in uninduced cells and their postmitotic neuronal derivatives, respectively expressing E- and N-cadherin. RhoA is thus influential on cell aggregation and cadherin expression during a sensitive time window that corresponds to the switch of E- to N-cadherin. Cell treatment with Y27632 inhibitor of Rho-associated-kinase ROCK, or advanced overexpression of Cdc42 by gene transfer of a constitutively active form of the protein reproduced C3 effects. RhoA-antisense RNA also reduced cadherin level and the size of cell aggregates, and increased the generation of fibroblast-like cells relative to neurons following neuroinduction. Colchicin, a microtubule disrupter, but not cytochalasin B actin poison, importantly decreased cadherin in neurodifferentiating cells. Overall, our results indicate that the RhoA/ROCK pathway regulates cadherin protein level and cell-cell interactions during neurodetermination, with an impact on the efficiency of the process. The effect on cadherin seems to involve microtubules. The importance of correct timing of RhoA and Cdc42 functional expression in neurogenesis is also raised.     

The SALM family of adhesion-like molecules forms heteromeric and homomeric complexes

Synaptic adhesion-like molecules (SALMs) are a newly discovered family of adhesion molecules that play roles in synapse formation and neurite outgrowth. The SALM family is comprised of five homologous molecules that are expressed largely in the central nervous system. SALMs 1-3 contain PDZ-binding domains, whereas SALMs 4 and 5 do not. We are interested in characterizing the interactions of the SALMs both among the individual members and with other binding partners. In the present study, we focused on the interactions formed by the five SALM members in rat brain and heterologous cells. In brain, we found that SALMs 1-3 strongly co-immunoprecipitated with each other, whereas SALMs 4 and 5 did not, suggesting that SALMs 4 and 5 mainly form homomeric complexes. In heterologous cells transfected with SALMs, co-immunoprecipitation studies showed that all five SALMs form heteromeric and homomeric complexes. We also determined if SALMs could form trans-cellular associations between transfected heterologous cells. Both SALMs 4 and 5 formed homophilic, but not heterophilic associations, whereas no trans associations were formed by the other SALMs. The ability of SALM4 to form trans interactions is due to its extracellular N terminus because chimeras of SALM4 N terminus and SALM2 C terminus can form trans interactions, whereas chimeras of SALM2 N terminus and SALM4 C terminus cannot. Co-culture experiments using HeLa cells and rat hippocampal neurons expressing the SALMs showed that SALM4 is recruited to points of contact between the cells. In neurons, these points of contact were seen in both axons and dendrites.     

神经钙粘着蛋白在P19神经元分化中的作用

利用ＲＴ－ＰＣＲ技术,我们检测Ｐ１９细胞体外神经元分化过程中神经钙粘着蛋白（Ｎ－ｃａｄｈｅｒｉｎ）的表达模式。结果显示,该基因在上述过程中存在上调和下调过程,与体内中枢神经系统发育过程的表达模式十分相近。在此基础上,我们将神经钙粘着蛋白基因ｃＤＮＡ全长转入Ｐ１９细胞,通过药物筛选,得到稳定表达钙粘着蛋白的细胞株。     

E-cadherin homophilic ligation directly signals through Rac and phosphatidylinositol 3-kinase to regulate adhesive contacts.

Classical cadherins mediate cell recognition and cohesion in many tissues of the body. It is increasingly apparent that dynamic cadherin contacts play key roles during morphogenesis and that a range of cell signals are activated as cells form contacts with one another. It has been difficult, however, to determine whether these signals represent direct downstream consequences of cadherin ligation or are juxtacrine signals that are activated when cadherin adhesion brings cell surfaces together but are not direct downstream targets of cadherin signaling. In this study, we used a functional cadherin ligand (hE/Fc) to directly test whether E-cadherin ligation regulates phosphatidylinositol 3-kinase (PI 3-kinase) and Rac signaling. We report that homophilic cadherin ligation recruits Rac to nascent adhesive contacts and specifically stimulates Rac signaling. Adhesion to hE/Fc also recruits PI 3-kinase to the cadherin complex, leading to the production of phosphatidylinositol 3,4,5-trisphosphate in nascent cadherin contacts. Rac activation involved an early phase, which was PI 3-kinase-independent, and a later amplification phase, which was inhibited by wortmannin. PI 3-kinase and Rac activity were necessary for productive adhesive contacts to form following initial homophilic ligation. We conclude that E-cadherin is a cellular receptor that is activated upon homophilic ligation to signal through PI 3-kinase and Rac. We propose that a key function of these cadherin-activated signals is to control adhesive contacts, probably via regulation of the actin cytoskeleton, which ultimately serves to mediate adhesive cell-cell recognition.     

Ultrastructural study of neurotensin immunoreactivity in the superficial laminae of the dorsal horn of the rat

Neurotensin immunoreactivity was identified in cell bodies, dendrites, spines, axons, terminals and varicosities in superficial laminae of rat spinal cord with the electron microscope. Unlabeled terminals synapsed with neurotensin-immunoreactive cell bodies, dendrites and spines. Presynaptic terminals contained round or pleomorphic vesicles and generally made symmetrical contacts with medium-sized neurotensin-containing dendrites in outer lamina II, and asymmetrical or symmetrical contacts with large and small dendrites and spines in inner lamina II. Neurotensin immunoreactive axons were unmyelinated, and their terminals were presynaptic to unlabeled dendrites and spines in laminae I and II. Terminals contained small, round, clear vesciles (31 nm) and occasional large granular vesicles (78 nm). Contacts in outer lamina II were evenly distributed among dendrites of various sizes and spines, whereas the majority of labeled terminals in inner lamina II made contacts onto small dendrites and spines. These findings indicate that neurotensin effects in rat spinal cord are mediated by axodendritic synapses, and that neurotensin cells at the inner and outer borders of lamina II contact dendrites of efferent neurons or other interneurons in the dorsal horn.     

Ultrastructure of synapses of the parietal and visceral ganglia of Helix pomatia

Types of synaptic contacts and peculiarities of their distribution in the neuropil of the parietal and visceral ganglia of the edible snail (Helix pomatia) CNS have been studied electron microscopically. Ultrastructure of dendrites and axons has been identified. Dendrites with spinous++ processes, polymorphism of synaptic contacts have been revealed. Besides axo-axonal synapses, axo-dendritic synapses are demonstrated on the trunks and on the spinous processes of the dendrites, as well as dendro-dendritic and serial synapses. Unevenness in distribution of synaptic contacts is shown in the neuropil. The areas of the greatest concentration of the synapses are the "synaptic fields". Peculiarities in distribution of the synaptic contacts are demonstrated in the parietal and visceral ganglia.     

Immunoelectron microscopic localization of the neural cell adhesion molecules L1 and N-CAM during postnatal development of the mouse cerebellum

The cellular and subcellular localization of the neural cell adhesion molecules L1 and N-CAM was studied by pre- and postembedding immunoelectron microscopic labeling procedures in the developing mouse cerebellar cortex. The salient features of the study are: L1 displays a previously unrecognized restricted expression by particular neuronal cell types (i.e., it is expressed by granule cells but not by stellate and basket cells) and by particular subcellular compartments (i.e., it is expressed on axons but not on dendrites or cell bodies of Purkinje cells). L1 is always expressed on fasciculating axons and on postmitotic, premigratory, and migrating granule cells at sites of neuron-neuron contact, but never at contact sites between neuron and glia, thus strengthening the view that L1 is not involved in granule cell migration as a neuron-glia adhesion molecule. While N-CAM antibodies reacting with the three major components of N-CAM (180, 140, and 120 kD) show a rather uniform labeling of all cell types, antibodies to the 180-kD component (N-CAM180) stain only the postmigratory granule cell bodies supporting the notion that N-CAM180, the N-CAM component with the longest cytoplasmic domain, is not expressed before stable cell contacts are formed. Furthermore, N-CAM180 is only transiently expressed on Purkinje cell dendrites. N-CAM is present in synapses on both pre- and post-synaptic membranes. L1 is expressed only preterminally and not in the subsynaptic membranes. These observations indicate an exquisite degree of fine tuning in adhesion molecule expression during neural development and suggest a rich combinatorial repertoire in the specification of cell surface contacts.     

Relais cells and afferent axons in the dorsal part of the lateral geniculate body in the albino rat under geometrical aspects]

1. The average volumes of dendritic domaines of relay neurons (P-neurons) were calculated and the quantitative relations to the neuronal elements situated in this area were investigated. Likewise we carried out measurements and calculations at the terminal parts of afferent axons, to find a conception concerning possible contacts between axons and P-neurons considering quantitative aspects. 2. The dendrites of one P-neuron are distributed in an area of about 0,008 mum3. In this area there are located somata of at least 120 other P-neurons and dendrites of altogether about 900 P-neurons. 3. The type-1-axons (cortical afferents) run almost linearly in the longitudinal system of the CGLd. Traversing a distance adequate to the diameter of a P-neuron (250 mum) the dendrites of 150 to 170 P-neurons may cross the course of one axon. At this distance the axon, however, has just set up about 50 boutons, thus synaptic contacts may be established with one third at most of the existing cells. A type-1-axon that is bifurcating in the entrance area into the CGLd is altogether of about 2000 mum in length and is able to develop about 420 presynaptic profiles. 4. The type-2-axons (retinal afferents) show a distinct terminal branching zone. The Golgi-Kopsch impregnated terminals of type-2a-axons are distributed in a space of 147000 mum3 capacity, the corresponding terminals of type-2b-axons in a space of 443000 mum3. The type-2a-axons having an average number of 23 boutons, may contact the dendritic branching zones of 25 P-neurons. There is a good reason to assume that type-2b-axons are in contact also with terminal dendritic parts of P-neurons. Thus the number of P-cells, which spread their dendrites into the terminal branching zone of one type-2b-axon may amount to 540. The average number of boutons of one type-2b-terminal, however, is only about 160. This means that synaptic contacts may be developed to the P-neurons-dendrites not exceeding 30% of them. 5. Various aspects of divergence of axon terminals in the albino rat's CGLd are discussed.