Osmotic stimulation causes structural plasticity of neurone-glia relationships of the oxytocin but not vasopressin secreting neurones in the hypothalamic supraoptic nucleus

A comparative quantitative analysis was carried out on identified supraoptic neurones of male and female Wistar and Long Evans rats under normal conditions and after chronic osmotic stimulation, and in homozygous Brattleboro rats suffering from diabetes insipidus. The neurones were identified by immunocytochemical or morphological means. Osmotic stimulation resulted in significant increases in the number and extent of direct neuronal appositions and in the number of presynaptic terminals contacting two neurosecretory cells simultaneously ("double" synapses). In the supraoptic nuclei of both sexes these increases were restricted to the oxytocin secreting neurones. In Brattleboro homozygous rats treated with vasopressin, the proportion of oxytocinergic neurones in apposition was not modified, but the number of appositions per soma profile decreased as did the incidence of "double" synapses. In nuclei of osmotically stimulated rats, increase in cell volume affected both types of neurosecretory cell and was accompanied by an increase of the absolute extent of glial coverage. However, the extent of glial coverage of the oxytocinergic neurones did not match the hypertrophy of the cells, resulting in a decrease in their relative glial coverage, compared to normal hydrated animals. The increased neuronal appositions, therefore, cannot result simply from a retraction of glial processes. The structural reorganization of the oxytocinergic system observed during chronic osmotic stimulation was as extensive as that observed at lactation. Moreover, the changes were as extensive in Wistar as in Brattleboro lactating rats, although the latter have an added osmotic stimulus. This implies that lactation and osmotic stimulation do not produce additive effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Morphological adaptability at neurosecretory axonal endings on the neurovascular contact zone of the rat neurohypophysis

To compare the effects of a variety of acute and chronic stimuli that bring about or terminate hormone release the ultrastructure of nerve terminal contact at the basal lamina of the neurohypophysial neurovascular contact zone was examined quantitatively in young adult rats of the following treatment groups: untreated virgin females, untreated male rats, prepartum (day 21 of gestation), postpartum (on the day of parturition), lactating (14 days of suckling), mothers 10 days after their pups were weaned, 48 h water-deprived males, males given 2% saline solution (dehydrated) for 10 days, males given 2% saline as described then given tap water to rehydrate for 2 or 5 weeks. Morphometric analysis of electron micrographs revealed that all stimuli leading to increased hormone release were accompanied by both increased occupation of the basal lamina by nerve terminals as well as decreased enclosure of neurosecretory processes by pituicyte cytoplasm. Neural occupation of the basal lamina remained significantly elevated 10 days post-weaning and at 2 weeks (but not 5 weeks) of rehydration following 10 days of dehydration. Pituicyte enclosure of neurosecretory axons had returned to control values in the postweaning and 5 week (but not 2 week) rehydrated animals. The mean length of individual nerve terminal contact with the basal lamina was found to increase under some, but not all, conditions associated with increased hormone release (i.e. parturition, acute and chronic dehydration, but not during lactation) and to decrease below control values in prepartum females and after 5 weeks of rehydration. During lactation, in contrast, the greater neural coverage of the basal lamina was accompanied by an increased number of terminals per unit length of basal lamina without an increase in the average contact length of the individual terminal.These data provide further evidence that neurohypophysial nerve terminal contact at the basal lamina and the relationship of pituicytes to neurosecretory processes can change under physiological conditions in a manner that is probably functionally related to controlling the contact area for hormone release.     

Evidence for dynamic interactions between pituicytes and neurosecretory axons in the rat

Several ultrastructural features of pituicytes as well as their relationship with neurosecretory axons were measured in neural lobes from rats either: non-deprived; water-deprived for 4, 12, or 24 h; or rehydrated for 12 or 24 h after an initial 24 h dehydration. A significant increase in pituicyte lipid bodies occurs with as little as 4 h of water deprivation. This is a time when several dehydration-related changes are known to occur in the somata of those neurosecretory cells sending axons to the neural lobe. Thus, increases in pituicyte lipid bodies may be related to the initiation of hormone release. In the neural lobes of water replete, non-deprived rats, pituicytes were found to contain neurosecretory axons completely enclosed by their cytoplasm. The number of these per unit area of cytoplasm decreased by 64% with 24 h of water deprivation and returned to normal levels with 24 h of rehydration. Since few of the enclosed axons were found to be degenerating, enclosure is unlikely to represent the early stages of phagocytosis.These findings suggest that during periods of little hormone secretion the neurosecretory axons are enclosed by the glial cells, but are released under conditions of increased hormone demand. This may provide the morphological framework for pituicyte involvement in inhibition and facilitation of hormone release from the neurohypophysis.     

Neurosecretory axon regeneration into intrahypothalamic neural lobe allografts: neurophysin immunohistochemistry and fine structure

Summary Neural lobe allografts placed stereotactically into the hypothalamo-neurohypophysial tract between the paraventricular and supraoptic nuclei were investigatd between 5 and 70 days post-transplantation (dpt). They contained temporally increasing numbers of neurophysin-positive axons. At the fine structural level, endogenous neurosecretory axons had virtually disappeared from successful (vascularized) grafts by 5 dpt. At this time, single host neurosecretory axons and especially numerous growth cones were associated with pituicyte processes and/or scalloped basal lamina scaffolds. Axon terminals containing neurosecretory granulated vesicles and microvesicles were present only occasionally at 5 dpt but became much more numerous subsequently. These terminals were associated with pituicytes and abutted the parenchymal basal lamina of pericapillary connective tissue spaces. In addition, beginning at 10 dpt, neurolemmocyte-like cells were associated with neurosecretory axons. At 70 dpt, the fine structural characteristics of grafted neural lobes were virtually indistinguishable from those of intact controls, except for the presence of occasional areas of more extensive connective tissue, nonfenestrated capillaries and neurolemmocyte-like cells.Dedicated to Prof. Th. H. Schiebler, Würzburg, on the occasion of his 65th birthdayThis investigation was supported by NSF grant BNS-84-04183 and Basic Research grant N. 1-900 from the March of Dimes Birth Defects Foundation     

Elevated extracellular potassium is associated with a reduced extracellular space in rat neural lobe in vitro

Summary Increased neural activity of neurosecretory cells is accompanied by large increases in extracellular K⁺. The possibility that elevations of this ion might involve fluid redistribution and thus affect the size of the extracellular space and the relationship between pituicytes and axons in the rat neural lobe was explored using rapid freezing and freeze-substitution. Neural lobes were incubated for 15 min before freezing either in a normal medium or one containing a 10 mM increase in KCl (high KCl), a 10 mM increase in KCl balanced by an equimolar reduction in NaCl (high KCl-low NaCl), or only a 10 mM reduction in NaCl (low NaCl). A quantitative assessment of the region of good fixation was made to determine the relative fractions occupied by axons, pituicytes and the extracellular space near the neurohaemal contact zone. In addition, the percentage of basal lamina contacted by pituicytes and axons was calculated, as was the degree of enclosure of axons by pituicytes.In neural lobes incubated in normal medium, the extracellular space accounted for approximately 30% of the cross-sectional area of the neuropil and could be divided into two domains: an extended perivascular space (28–29% of total area); and a narrow (approximately 24 nm; approximately 1% of total) space between closely apposed neurosecretory processes or between these processes and pituicytes. Pituicytes occupied almost 60% of the basal lamina at the neurohaemal contact zone, while axons occupied approximately 20%. Neural lobes incubated in either the high KCl solution, or in the high KCl-low NaCl solution, exhibited a significantly reduced extracellular space, to about 20% of the total area, or a reduction from controls of about one-third. The reduction was complemented by an increased area occupied by axons plus pituicytes. In the high KCl group, the contribution of the narrow spaces (22–24 nm) between apposed processes to the total extracellular space was greatly increased. The group exposed to low NaCl showed high variability in the size of extracellular space, and was thus not significantly different from any other group. No changes in any group were observed in the enclosure of axons by pituicytes, or in the relative amounts of axon and pituicyte apposition to the basal lamina.The subsequent buffering of K⁺ and other ions during periods of increased neuronal activity may be affected by changes in the extracellular space, thereby influencing stimulus-secretion coupling. A shrinkage of the extracellular space and the relative increase in the narrow spaces between processes initiated by elevated K⁺ could also alter the diffusion properties of the neural lobe.     

The effects of the loss of target cells upon photoreceptor inputs in the fly''s optic lobe

Summary The sensitivity of sensory neurons to target cell denervation varies in the CNS. We have examined the effects of surgically interrupting the output axons of the first optic neuropil, or lamina, in the optic lobe of the fly (Musca domestica), upon the receptor terminal inputs to the lamina. Two of the output interneurons are the monopolar cells L1 and L2, which are found as a pair in each of the unit modules or cartridges of the lamina neuropil. The lamina axons of LI and L2 degenerate rapidly (within 0.5 h) in a retrograde direction from their lesion site, but there is no sign of retrograde transneuronal degeneration to the receptor terminals, across the input synapse. At each of these synaptic sites, L1 and L2 are invariable contributors to two of the four elements of a postsynaptic tetrad. Not only do the receptor terminals persist, but the presynaptic ribbons at the tetrad sites do also, opposite the degenerated spines of L1 and L2, indicating their lack of target dependence at least over the longest period of post-lesion recovery (48 h) examined. The areal density of presynaptic sites was conserved in the face of the degenerative loss of L1 and L2, as were the numbers of capitate projections (glial invaginations into receptor terminals). The stability of both synaptic density and capitate projection number indicates that they are predominately influenced by the receptor terminals, which are still intact. A reduction in the number of mitochondrial profiles was one of the few observed changes in the receptor terminals. The results reflect the autonomy which the terminals have, during development, from their interneurons; they especially reflect the role of the terminals in the adult, in maintaining the presynaptic site of their afferent synapses, the tetrads.     

Neuronal/glial plasticity in the supraoptic dendritic zone: Dendritic bundling and double synapse formation at parturition

The magnocellular neurosecretory cells of the supraoptic nucleus increase production and release of oxytocin and/or vasopressin under such conditions as parturition, lactation and dehydration. These stimuli have been shown to result in increased direct apposition of neuronal membranes and the formation of double synapses (one presynaptic terminal contacting two postsynaptic elements) within the supraoptic nucleus at the level of the cell bodies. These morphological changes are due to the retraction of the thin glial processes which are normally interposed between adjacent neurons. The present study was undertaken to ascertain whether, and to what extent, neuronal/glial plasticity occurs in the dendritic zone (i.e. the ventral glial laminar area) of the supraoptic nucleus. The instances of two or more dendrites with membrane in direct apposition (dendritic bundles), the number of dendrites per bundle, the amount of dendritic membrane in direct apposition and the percentage of dendrites contacted by double synapses were quantified at the ultrastructural level in virgin female, prepartum (21 days of gestation), postpartum (day of parturition) and lactating rats. All parameters measured varied significantly with the hormone demand states created by pregnancy and lactation, apparently due to glial retraction. Moreover, in the 2–24 h period between pre- and postpartum there was a significant increase in the number of dendrites per bundle, dendritic membrane in direct apposition and the percentage of dendrites contacted by double synapses. This time course corresponds to the known increased release of oxytocin and vasopressin at parturition.These findings constitute the first demonstration that dendritic bundles and double synapses occur in the ventral glial lamina/dendritic zone of the supraoptic nucleus and vary under the physiological conditions of pregnancy, parturition and lactation.     

Definitive evidence for the existence of morphological plasticity in the external zone of the median eminence during the rat estrous cycle: implication of neuro-glio-endothelial interactions in gonadotropin-releasing hormone release

Despite intense investigation, the demonstration of morphological plasticity in the external zone of the median eminence concerning the gonadotropin-releasing hormone system has never been reported. In this study, we investigate whether dynamic transformations of the gonadotropin-releasing hormone nerve terminals and/or tanycytes in the external zone of the median eminence of the hypothalamus occurred during the rat estrous cycle, by following individual gonadotropin-releasing hormone-immunoreactive nerve terminals on serial ultrathin sections observed by electron microscopy. Female rats were killed at 16.00 diestrus II (n = 3), i.e. when estrogen levels are basal and gonadotropin-releasing hormone release is low, and at 16.00 proestrus (n = 4), i.e. when estrogen levels peak and the preovulatory gonadotropin-releasing hormone surge occurs. Our results show that, in the median eminence obtained from proestrus rats, 12+/-2% of the gonadotropin-releasing hormone nerve terminals were observed to make physical contact with the parenchymatous basal lamina, i.e. the pericapillary space. In the median eminence obtained from diestrus II rats, no contacts were observed. On proestrus, numerous physical contacts between gonadotropin-releasing hormone nerve terminals and the basal lamina occurred by evagination of the basal lamina and/or by emerging processes from gonadotropin-releasing hormone nerve terminals. The quantification of the evagination of the basal lamina revealed that the basal lamina was at least twofold more tortuous in appearance during proestrus. These results demonstrate for the first time the existence of dynamic plastic changes in the external zone of the median eminence, allowing gonadotropin-releasing hormone nerve terminals to contact the pericapillary space on the day of proestrus, thus facilitating the release of the neurohormone into the pituitary portal blood.     

Simultaneous changes of the perivascular contact area and HIMOT activity in the pineal organ after bilateral adrenalectomy in the rat

Summary In the pineal organ of the female rat, proportional changes in the area of contact of pinealocyte processes and glial processes with the perivascular space were found after bilateral adrenalectomy. The contact area was evaluated by measuring the length of pinealocyte and glial cell membranes directly abutting on the basal lamina. In the normal female rat, 40% of the contact area is occupied by pinealocyte and 60% by glial cell processes. Fourteen days after bilateral adrenalectomy, this proportion is reversed. In addition, cell counts demonstrate that more pinealocytes gain access to the pericapillary space due to the experimental conditions.In order to prove whether or not these results indicate an increase of pineal endocrine activity, the melatonin-forming enzyme hydroxyindole-O-methyltransferase (HIOMT, E.C. 2.1.1.4) was assayed. After bilateral adrenalectomy the HIOMT activity was found to significantly increase.The authors wish to dedicate this paper to Professor Wolfgang Bargmann on the occasion of his 70th birthdayThis paper includes results of the Doctor's Thesis of Marlies Schmitter at the Medical Faculty of BonnSupported by grants from the Landesamt für Forschung, Nordrhein-Westfalen (BRD) and the Deutsche Forschungsgemeinschaft     

Immunoelectronhistochemical evidence for innervation of brain microvessels by vasopressin-immunoreactive neurons in the rat

Peroxidase-antiperoxidase (PAP) immunocytochemistry at the electron microscopic level was used to describe the fine structural characteristics of vascular connections between vasopressin (VP)-immunoreactive neuronal elements and cerebral microvessels in the rat. In the majority of connections, somata or neural processes (mainly dendrites) showing VP-like immunoreactivity were separated from the vessel wall by thin glial processes. In addition, some VP-positive elements could establish direct contacts with the basal lamina of the endothelium or of a pericyte associated with the capillary bed. The findings provide immunocytochemical evidence that the vasopressinergic neuronal elements can directly innervate microvessels in the brain and thereby participate in regulating the local permeability of and the flow through the cerebral microvessels.     

大鼠脑组织细胞培养的形态学观察

为观察原代培养 SD大鼠大脑组织 ,包括神经干细胞在内的各种细胞的形态 ,取新生大鼠 ,无菌操作下取出整个大脑 ,制备成单细胞悬液 ,接种培养 ,免疫细胞化学鉴定各类细胞的同时用光镜和扫描电镜对不同阶段和种类的细胞进行形态学观察。结果显示 :在体外培养出神经元、胶质细胞和神经干细胞 ;神经细胞在体外的发育时程跟体内基本一致 ,神经干细胞在体外 2 0 d左右分化成熟 ,获取了神经细胞和干细胞体外培养的光镜和扫描电镜形态。结果提示 ,成体神经细胞体外分离、培养的条件关键点在于尽可能贴近自然 ,由此可保证细胞培养的质量 ,获得可靠的神经干细胞、神经元和胶质细胞。为各类神经细胞提供了形态学资料。     

Altered synaptic circuitry in the human temporal neocortex removed from epileptic patients

 Quantitative electron microscopic methods were used to study possible alterations in presumptive excitatory and inhibitory synaptic circuits in human neocortex removed from patients with intractable temporal lobe epilepsy. Synaptic density was compared between normal and abnormal regions as identified by Nissl staining and immunocytochemistry for the Ca²⁺-binding protein parvalbumin (PV). The normal regions showed a normal cytoarchitecture and normal pattern of staining for PV, whereas the abnormal regions displayed focal neuronal cell loss and a decrease in immunostaining for PV. In the abnormal regions the overall synaptic density (per 100 μm² and per mm³) was approximately 30% higher than in normal regions, which corresponded to an increase of approximately 300 million synapses per mm³. The number of excitatory and inhibitory synapses was significantly higher and lower, respectively, than in normal regions. We suggest that these changes are a result of a focal sprouting of excitatory axon terminals and loss of inhibitory terminals which leads to hyperexcitatory synaptic circuits. These circuits may represent a neural substrate for the initiation or propagation of seizure activity in human epileptogenic neocortex. Received: 5 July 1996 / Accepted: 13 September 1996     

Myocardial capillaries in the fetal and the neonatal rat: A morphometric analysis of the maturing myocardial capillary bed

Developing myocardial capillaries from 16-day-gestation fetus to adult undergo several morphological changes including a thinning of the lateral extensions of the capillary endothelial cells, the formation of a basal lamina, and an increase in the number of plasmalemmal vesicles. A decrease in the extracellular space, an increase in the number of capillaries, and a decrease in the capillary diameter were also observed during the developmental period. In view of these ultrastructural changes, a morphometric analysis was made on the developing myocardial wall to demonstrate specific quantitative changes. The volumes which were occupied by capillary endothelial cells, capillary lumina, extracellular space, and myocardial myocytes within a reference volume of myocardium were measured; and we found that 8% of the reference myocardial volume was occupied by capillary endothelial cells, 85% was occupied by myocardial myocytes, 4% was occupied by capillary lumina, and, except for a significant change in extracellular space at 16 days gestation, 3% was occupied by extracellular space. Each volume ratio was found to be nearly constant throughout the studied period. In contrast to this constancy in the volume ratios, other parameters which were measured demonstrated significant changes during the developmental period studied. These overall changes include a 135% increase in capillary density, a 63% increase in luminal surface area of capillary endothelial cells, a 24% decrease in capillary diameter, a 12% decrease in diffusion distance, and a 35% decrease in the diameter of the erythrocyte population. The decrease in capillary diameter occurs concomitantly with and may be correlated to the decrease in erythrocyte diameter. Also, the increasing number of capillaries offset the effect of the decrease in capillary diameter, resulting in constant volume ratios. This constancy in the volumes of the measured myocardial compartments during development, despite the considerable changes in morphology and in the other measured parameters which are occurring in the myocardial wall, can be interpreted to mean that some functional constraints are operating to maintain capillary-to-myocardium volume ratios within very narrow limits.     

Comparative immunohistochemical study of the presence of glial fibrillary acidic protein in the pituitary of several vertebrates

The presence and distribution of the astrocytic marker protein GFAP (glial fibrillary acidic protein) in the pituitaries of several mammalian as well as of some submammalian vertebrates were examined immunohistochemically. Our study revealed that GFAP-immunoreactive pituicytes, probably reflecting the presence of the filament-rich fibrous type of pituicyte, are a common feature of the mammalian neural lobe. Moreover, interspecific and interindividual differences of the neurohypophyseal immunostaining could be observed. In the distal neurohypophysis of some submammalian vertebrates, processes of ependymal glia showed GFAP-like immunoreactivity. Our results are in agreement with the well established evolutionary stability of GFAP elsewhere in the brain. In contrast to the neurohypophysis, GFAP-positive cells within the intermediate lobe were inconstantly present in only some species. They may be derived from neurohypophyseal glia. Folliculo-stellate cells of the adenohypophyseal pars distalis were not stained.     

Nerve growth factor receptor in neural lobe of rat pituitary gland: immunohistochemical localization, biochemical characterization and regulation

Summary Nerve growth factor-receptor immunoreactivity was detected in the neural lobe of the pituitary gland in developing and adult rats of both sexes. The presence of nerve growth factor receptor in the neural lobe was further verified by a quantitative¹²⁵I-nerve growth factor/crosslink/immunoprecipitation assay and subsequent visualization by SDS-PAGE autoradiography. Nerve growth factor-receptor immunoreactivity was detected in the neural lobe of postnatal 5-day-old rats, had increased by 2 months and was much higher in 1-year-old rats. In 2-month-old rats, no immunoreactivity was observed in anterior or intermediate lobes. Pituitary stalk transection in young adult rats greatly increased the expression of nerve growth factor-receptor immunoreactivity in the neural lobe, although the staining pattern remained the same. This increase began 3 days after surgery, and reached peak levels at approximately 15 days. Other physiological or non-physiological changes did not alter the nerve growth factor-receptor immunoreactivity in the neural lobe; these changes included dehydration, pregnancy and lactation, castration of male rats, bilateral superior cervical ganglionectomy and intraventricular injection of colchicine. Intravenously injected¹²⁵I-nerve growth factor was specifically accumulated in both normal and denervated neural lobe. Nerve growth factor-receptor immunohistochemical electron microscopy showed that the receptor-positive cells are fusiform and found both inside and outside the basal lamina that delimits the neural lobe parenchyma. Based upon the anatomical localization, morphology and response to axotomy, we identify, at least the perivascular component, as microglia. These data suggest a role for nerve growth factor and/or nerve growth factor receptor in microglial function.     

Effect of age on blood vessels and neurovascular appositions in the rat dentate fascia

Rats aged 3, 9, 24 and 30 months were used in this study. We show increased basal lamina thickening and increased mitochondrial presence in walls of capillaries and not in walls of large vessel populations with age. This suggests that age selectively affects capillary structure. Ultrastructural differences between capillaries and two types of large vessels are reported and discussed in terms of their probable functional significance. In particular it was noted that there are more axon terminals, axons and dendrites adjacent to capillaries than to large vessels and that this was unaffected by increasing age. It is not clear whether the proximity of neuronal processes to a vessel wall serves a function, however, the larger number adjacent to capillaries than to large vessels indicates a more significant role for them in capillary rather than in large vessel function. Since increasing age did not alter the number of neuronal processes adjacent to vessels, age-related compromises in vessel function may be unrelated to neuronal regulation. The age-related changes are discussed as possible vascular markers for the aging brain.     

Quantitative morphological changes in neurons and glia in the frontal lobe of the aging rat

The quantitative morphological changes in neurons and glia during the aging process were analyzed in the different cortical layers, grouped as I, II–IV, V, and VI, of the frontal cortex of the rat. The parameters analyzed were cortical volume, neuronal density, glial density, and neuronal soma and nucleus areas. No changes with age were found in the volume of the layers, in neuronal density (with the exception of layer I), or in the area of the neuronal soma. However, older animals showed a 10 to 20% increase in glial density, depending on the layer studied. In addition, there was an age-related decrease in the area of the neuronal nucleus in layers II–IV, V, and VI. These results support the idea that the aging frontal cortex undergoes structural changes that may be involved in the morphological basis of memory and cognitive impairments characteristic of aging. © 1993 Wiley-Liss, Inc.     

Destruction of meningeal cells over the newborn hamster cerebellum with 6-hydroxydopamine prevents foliation and lamination in the rostral cerebellum

Intracisternal injection of 30 micrograms 6-hydroxydopamine was used to destroy meningeal cells in the newborn hamster. After 20 or 30 days the cerebella of treated animals showed severe morphological alterations including: an absence of distinct folia anterior to the primary fissure; a disruption of lamination in the same region by the displacement of both Purkinje cells and cerebellar interneurons; a reduction in size and frequency of branching of the medullary tree with anomalous anterobasal branches and splaying; reductions in the area of the molecular layer, the total area occupied by granule cells, the length of the pial surface and the length of the Purkinje cell layer of 29, 21, 57 and 27%, respectively; disorganization of the radially organized glial scaffold by outgrowth of Bergmann glial fibers and displacement of their cell bodies, the Golgi epithelial cells, and anomalous orientation, polarity, size and branching frequency of Purkinje cell dendritic trees. These findings support our earlier hypothesis that the initial destruction of meningeal cells destabilizes the cerebellar surface (basal lamina and glia limitans superficialis) and disorganizes the glial scaffold, while the neuronal cerebellar malformations are secondary to this glial defect.     

Ultrastructural changes of the central scalloped (C1) primary afferent endings of synaptic glomeruli in the substantia gelatinosa Rolandi of the rat after peripheral neurotomy

Summary Fine structural changes were observed in the dark scalloped central C₁ terminals of type I synaptic glomeruli in spinal cord segments C6–C7 of the rat 3 days after cutting the three main forelimb nerves. Twenty-six per cent of the C₁ terminals occurring on the ipsilateral side showed a lighter appearance due to a decrease in the number of synaptic vesicles. The number of synaptic vesicles per unit section area was only 42% of that present in normal C₁ terminals on the contralateral side. The number of synaptic contacts of C₁ terminals with the profiles surrounding them in each glomerulus was diminished and glial envelopment was increased to 15% of C₁ terminal contour. Up to day 12, vesicle and synaptic losses were gradually aggravated and glial apposition was increased, but no obvious signs of glial engulfment were observed. From day 3 to day 12, altered C₁ terminals increased in number, while those that appeared normal decreased. The latter had disappeared at day 12 and the altered ones at day 15, and from this stage type I glomeruli were no longer present on the treated side. The lack of electron-dense degenerative bouton changes characteristic of Wallerian degeneration offers an explanation for the lack of or minimal amount of argyrophilic structures which has been found consistently in the substantia gelatinosa during transganglionic degeneration. The gradual decay of the C₁ terminals raises the question of their fate. Future studies with the use of a stable marker might provide an answer.     

Differential expression of two adhesion molecules of the immunoglobulin superfamily, F3 and polysialylated NCAM, in hypothalamic magnocellular neurones capable of plasticity

The adult hypothalamo-neurohypophysial system undergoes activity-dependent, reversible morphological changes which result in reduced astrocytic coverage of its neurones and an increase in their synaptic contacts. Our recent observations show that neurones and glia of the hypothalamo-neurohypophysial system continue to express 'embryonic' molecular features which may underlie their capacity to undergo such plasticity. These include expression of cell surface molecules like the glycosyl phosphatidyl inositol (GPI)-linked glycoprotein F3, which intervenes in axonal outgrowth, and the polysialylated isoform of the neural cell adhesion molecule (PSA-NCAM), which reduces cell adhesion and promotes dynamic cell interactions. F3 is colocalised with vasopressin and oxytocin hormones in neurosecretory granules and follows an activity-dependent, regulated pathway for surface expression on neurohypophysial axons. In contrast, PSA-NCAM appears to follow a constitutive pathway, independent of the activity of the hypothalamo-neurohypophysial system, for expression on axonal and glial surfaces, in the hypothalamic magnocellular nuclei and in the neurohypophysis. The role of F3 remains to be determined but in view of its presumptive functions during development, we propose that it promotes remodelling of neurosecretory terminals. On the other hand, we provide direct evidence that surface expression of PSA on NCAM is essential to morphological plasticity since its specific enzymatic degradation in vivo inhibited the neuronal-glial and synaptic changes normally induced by stimulation of secretion from the hypothalamo-neurohypophysial system.