Non-cholinergic afferents determine the distribution of the cholinergic septohippocampal projection: a study of the AChE staining pattern in the rat fascia dentata and hippocampus after lesions,X-irradiation,and intracerebral grafting

Summary The acetylcholinesterase (AChE) activity of the rat hippocampus and fascia dentata depends on an intact septohippocampal connection, and histochemical staining for AChE is commonly used to monitor the distribution of the cholinergic septohippocampal projection. It is also characteristic that the laminae of low or moderate to dense AChE staining in the hippocampus and fascia dentata coincide with the terminal fields of the major non-cholinergic, afferent pathways. While studying lesion-induced collateral sprouting and aberrant axonal growth of these pathways we observed that the AChE staining pattern changed in accordance with the reorganized distribution of the non-cholinergic pathways, and this occurred even without direct interfering with the septohippocampal projection itself. Widening and narrowing of the medial perforant path and mossy fiber terminal zones thus resulted in corresponding changes in the bands of AChE staining normally associated with these zones. Expansion of the commissural-associational hippocampodentate projections and the lateral perforant path was in a similar way paralleled by a widening of the AChE-poor zones which normally overlap with the termination of these projections. Observations of the same kind were made in intracerebral transplants of fascia dentata innervated by various host afferents, and in rats subjected to neonatal X-irradiation, where the mossy fiber projection is reduced and aberrant perforant pathways project into CA3 due to a reduced formation of granule cells. The observed sets of changes with linkage between the different noncholinergic projections and the activity of AChE in their respective terminal fields were accordingly reproduced under several different experimental conditions. It could not be explained alone by interaction between the septal afferents and their target cells. We therefore conclude that the density and laminar distribution of the AChE activities within the hippocampus and fascia dentata are determined at least in part by the major afferent, noncholinergic nerve connections. We suggest that the effect occurs through direct axonal interaction or through changes in the receptiveness of the common dentate and hippocampal target cells.     

Somatosensory cross-modal plasticity in the superior colliculus of visually deafferented rats

The effects of neonatal visual deafferentation on the final adult pattern of cortico-collicular connections from the rat primary somatosensory cortex barrel field were studied by injecting an anterograde tracer (BDA) into different locations of the barrel cortex. Collicular afferents originating in the barrel cortex normally end in the intermediate collicular strata (SGI and SAI). However, neonatal visual deafferentation caused an invasion of abundant somatosensory cortical afferents into the lateral portions of the superficial collicular strata (SGS and SO). Moreover, anterograde-labelled fibers in the intermediate strata were more densely packed in visually deafferented animals. In order to study the activity of the altered somatosensory cortico-collicular connection, the effects of two different types of whisker stimuli on c-fos expression in the SC were analyzed (apomorphine treatment and enriched environment exploration). In stimulated control animals, c-fos expression was clearly evident in neurons of the intermediate layers 2 h after whisker stimulation. Similar stimulation in adult animals that underwent neonatal visual deafferentation triggered higher levels of c-fos expression in the superficial collicular layers that were invaded by cortico-collicular axonal branches. In exploration experiments, increased levels of c-fos expression were also detected in lateral parts of the intermediate layers of visually deafferented animals. These results suggest that the ascending fibers of somatosensory cortical origin can recruit deafferented superficial collicular neurons that enabling them to participate in extravisual behavioural responses mediated by collicular circuits.     

Compensatory increase of responses to nerve stimulation of the partially denervated rat urinary bladder

The rat urinary bladder was deprived of half of its innervation by removing the pelvic ganglion on one side. The motor responses of such a partially denervated bladder to stimulation of the pelvic nerve on the other side were examined I week, 1 month and 2 months postoperatively. On all three occasions the increase in pressure of the operated bladder was larger than that of the control bladder; the enlargement was most marked 2 months after operation. The responses were further enlarged by esenne, and markedly reduced by atropine. The present results combined with those of previous investigations, showing a rapid recovery in the activity of the acetylcholine forming enzyme from a reduced level and a transient supersensitivity to chemical stimuli after unilateral removal of the pelvic ganglion. suggest that the enlarged responses to nerve stimulation 1 week postoperatively are mainly due to sensitization, while those observed at the later stages are due to collateral sprouting from the cholinergic nerve fibres of the intact pelvic nerve.     

Preservation of the entire population of normally transient ipsilaterally projecting retinal ganglion cells by neonatal lesions in the rat

Summary The number of ipsilaterally projecting retinal ganglion cells (IPRGCs) in developing normal rats and rats which received unilateral thalamic lesion and monocular enucleation at birth was studied using wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) as a retrograde neuronal marker. The results showed that the number of IPRGCs labelled in day-21 rats which received lesions at birth was comparable to the highest number of IPRGCs observed in normal rats on day 0 (day of birth). These results suggest that the entire population of IPRGCs which had their axons already grown in or near to their target structures on day 0 can be rescued by neonatal lesions.     

On the role of vestibulo-ocular reflex plasticity in recovery after unilateral peripheral vestibular lesions

Summary Although adaptive plasticity is a wellknown feature of the vestibulo-ocular reflex (VOR), deficits in VOR performance after unilateral labyrinthectomy are poorly compensated in a large percentage of cats. To assess whether VOR plastic capabilities are affected by labyrinthectomy, forced oscillation in front of a patterned surround was imposed in unilaterally labyrinthectomized cats. This experimental paradigm has been shown to be very effective in inducing adaptive VOR gain changes in intact animals. We demonstrate that plasticity of VOR gain is still present both in acute and chronic stages following vestibular lesions. By contrast, forced oscillation did not significantly alter the lesion-induced asymmetry of responses. We conclude that VOR gain control mechanisms are not used to their fullest possible extent in a large percentage of animals suffering unilateral vestibular damage.Supported by grants nos. 3.228.82 and 3.403.83 from the Swiss National Science Foundation and Dr. Erik Slack-Gyr FoundationProf. Precht died on March 12, 1985     

Rostrocaudal and lateromedial density distributions of superior colliculus neurons projecting in the predorsal bundle and to the spinal cord: a retrograde HRP study in the cat

Summary Efferent neurons of the cat superior colliculus (SC) which project in the predorsal bundle (PDB) and to the spinal cord (PDB neurons) form a major pathway by which the SC controls the changes of the direction of gaze in response to stimuli of visual and other modalities. Knowledge of rostrocaudal and lateromedial density distributions of different groups of PDB neurons within the SC is necessary to analyse their relationships with the topography of sensory and motor maps. Density gradients may also bear on the efficacy of connections originating from topographically different collicular regions. In the present study, large injections of HRP/ WGA-HRP were made in the C1 segment of the spinal cord and in the pontobulbar tegmentum. Judged by several morphological criteria, axons of passage, including those not subjected to a direct mechanical damage, were participating in the uptake of tracers. Therefore, labeled SC neurons corresponded to the nearly total populations of contralaterally projecting tectospinal neurons (TSNs) and neurons projecting in the PDB, respectively. Subtraction of the TSN density map from that of the whole PDB population was used to infer the distribution of tectal neurons terminating in the rhombencephalic tegmentum (TRhN). This subtotal labeling method proved useful in resolving the contradictions between the earlier HRP studies on the TSN and TRhN topography. The following density distributions were obtained for different groups of PDB neurons: 1) The mean TSN density is more than two times higher in the lateral half of the SC, representing the lower visual field. In this region the density remains constant from rostral to caudal, i.e., from the representation of vertical meridian to large contralateral azimuths. In the medial half, the average density decreases from rostral to caudal. Consequently, TSNs do not show the caudalward increment predicted by the higher efficacy of caudal stimulation points in eliciting head movements. 2) The distribution of PDB neurons is symmetrical with respect to the representation of the horizontal meridian. It is close to homogeneous at all azimuths of the retinotopic map and within the zone limited by small (10–15°) upward and downward elevations. There are clear density decrements towards the representation of greater elevations. We conclude that the assumption of homogeneous distribution of efferent neurons, made in the models of the primate SC, is valid in the cat, but only for the whole population of neurons projecting in the PDB and within the area representing the proximity of the horizontal meridian. The same restrictions apply to the validity of the translation invariance principle. 3) The distribution of TRhNs, obtained by subtraction, shows a tendency to higher densities in the caudal half of the SC, and a clear bias towards its medial zone, including the representation of the horizontal meridian and upper visual field. The different types of asymmetry in TRhN and TSN populations may be related to different types of head movements depending, respectively, on distant and near stimuli in the upper and lower visual fields.Abbreviations NRTP nucl. reticularis tegmenti pontis - PDB predorsal bundle - PPRF paramedian pontine reticular formation - RGc nucl. reticularis gigantocellularis - Rmc nucl. reticularis magnocellularis - RPc nucl. reticularis pontis caudalis - RPo nucl. reticularis pontis oralis - SGI stratum griseum intermediale - SGP deeper layers, beginning from stratum album intermediale - SC superior colliculus - TRhN tectorhombencephalic neuron with crossed projection - TSN tectospinal neuron On leave from: Laboratoire de Neurophysiologie, Faculté de Médecine, Université de Louvain, Belgium     

Effects of neonatal intraocular colchicine on synaptogenesis and on the retention of the ipsilateral retinofugal projection within the superior colliculus

Summary A normally transient ipsilateral retinofugal projection exists in the rat but is retained following eye removal because of the loss of competitive interaction between crossed and uncrossed fibers. To further explore this phenomenon, colchicine (10^–3M) was injected into the right eye of newborn albino rats to partially suppress axonal transport in optic fibers, alter the developmental time course of retinofugal synaptic terminals and determine if this would in turn extend the period of survival of the ipsilateral projection. Measurements of the number of fibers in the nerve were also made to insure that colchicine was not lethal to the retinofugal projection. Projections into the superior colliculus were demonstrated by anterograde movement of HRP from the left eye. TMB histochemistry revealed dense labeling of the contralateral retino-recipient layers at 5 dpn in untreated or saline-injected controls. The ipsilateral projection was seen as a lighter band of activity across the colliculus which was most concentrated in the antero-medial quadrant. This pathway was transient and degenerated by 10 dpn, except for a few antero-medial fibers. Animals treated with colchicine demonstrated a retention of this pathway through 20 dpn. A concomitant quantitative analysis of synaptic development within the superior colliculus revealed populations of boutons with round (R) and flattened (F) vesicles, as well as multiple junctional (MJ) and serial (S) complexes, most of which were specialized R boutons. The various synaptic categories displayed specific ratios unique to the different stages of maturation. Intraocular colchicine reduced the ratio of R, MJ and S boutons to F terminals between 5–15 dpn (P < 0.01). By 20 dpn, the proportions of MJ and S boutons remained depressed but the normal ratio of R to F boutons was restored. Areal determinations of each synaptic profile included in the counts revealed a significant reduction in the size of MJ synaptic profiles examined in colchicine-treated animals and this may have been reflected in the slight loss of tectal volume (6–9%). Removal of the left eye and assessment of degenerating boutons showed that the expanded ipsilateral projection was not sufficiently dense to produce such a restoration. It thus appears that colchicine delayed the growth of the R population, but the effect was reversible and this category of boutons continued to develop, albeit on a later time course. Continued depression of MJ and S boutons suggests that suppression of the rate and quantity of axonally-transported substances retards the final stages of tectal synaptic differentiation, reduces their competitive advantage and allows the retention of the ipsilateral optic projection.     

Enhanced sprouting of retinotectal fibers after early superior colliculus lesions in hamsters treated with gangliosides

Summary The effects of exogenous gangliosides on sprouting of optic tract axons was studied in hamsters which, after a right tectal lesion on the day after birth (P1), had an abnormal retinotectal projection from the left eye to the left superior colliculus (SC). Sprouting of these axons was induced by removing the competing input by right eye removal on postnatal day 9 (P9). Intraperitoneal G_M1, given daily and started on P9, significantly stimulated the sprouting response. This was demonstrated by Fink-Heimer silver staining of anterograde axonal degeneration three days after the left eye was removed on P36. Terminal fields in the left SC were, in average, twice as large compared to controls. An estimate of the total number of terminals (silver stained particles) revealed a value of 7.9×10⁶ for G_M1 and 3.2×10⁶ for control hamsters, respectively. Diencephalic structures which also receive collateral input from the sprouting optic tract did not show any alterations in the size of the terminal field due to G_M1-treatment, suggesting that, in vivo, gangliosides fail to initiate sprouting in areas that have not previously been denervated. Unexpectedly, G_M1-treated hamsters also had significantly smaller right SC damage and less left damage near the midline. Subsequent reanalysis of the data based on a lesion-matching procedure indicates that effects on reducing atrophy were independent of the G_M1-enhanced sprouting of retinofugal axons. These findings provide the first direct evidence that exogenous G_M1 stimulates lesion-induced axon sprouting in the mammalian brain.     

葡萄糖、精氨酸影响新生大鼠胰B细胞群的形态定量研究

目的 :研究葡萄糖、精氨酸对新生大鼠胰 B细胞群的影响。方法 :选用 Wistar新生大鼠 ,自出生后第 2日起腹腔注射葡萄糖加精氨酸 ,共 6天。分别于出生后第 10天、2 0天剖腹取胰腺 ,进行常规 HE及免疫组织化学 (PAP)染色 ,显示胰岛及 B细胞。并结合图像分析仪测量胰岛及 B细胞。并结合图像分析仪测量胰岛及 B细胞的直径。结果 :生后 2 0天 ,实验组大鼠胰 B细胞群较第 10天的明显增大 ,而对照组 B细胞群却较第 10天显著缩小 ;第 2 0天两组胰岛直径均较第 10天的小 ,但以对照组的变化明显。结论 :在葡萄糖、精氨酸的作用下 ,新生大鼠胰 B细胞群及胰岛其它内分泌细胞增生     

Evidence for the sprouting of the associational fibers to the dentate gyrus following removal of the commissural afferents in adult rats

Summary Following chronic removal of the commissural afferents to the dentate gyrus in adult rats, there is a reorganization of the associational afferents (which are normally co-extensive in their distribution with the commissural fibers) in the inner third of the molecular layer. This has been demonstrated by injecting small amounts of ³H-proline into the hilar region of the dentate gyrus at about the middle of its septotemporal extent (so as to label the cells that give rise to the associational afferents) in normal 24 to 28 week-old rats, and in animals of the same age in which the contralateral hippocampus had been destroyed some 12 to 16 weeks previously. In autoradiographs of the control brains the ratio of the number of silver grains seen over the suprapyramidal blade to that found over the infrapyramidal blade is close to 2:1. Following removal of the commissural input to the dentate gyrus the corresponding ratio is 1:1. Since there is now good evidence to indicate that grain density ratios of this kind accurately reflect the relative numbers of synapses formed by the associational fibers in the two blades, these observations make it clear that even in adult animals the associational fibers are capable of reactive synaptogenesis in response to the removal of the commissural afferents.This work was supported in part by grants NS 10943 and EY-01255 from the National Institutes of Health and DA-00259 from ADAMAH, and was carried out while D.D.M.O'L. was in receipt of a pre-doctoral fellowship from a Neurobiology Training Grant 5-732-NSO 7071     

Aberrant retinal projections to midbrain targets mediate spared visual orienting function in hamsters with neonatal lesions of superior colliculus

Summary Rodents, cats, and most nonmammalian vertebrates with bilateral tectal deafferentation or ablation in adulthood are extremely deficient at orienting to visual stimuli; yet animals with neonatal lesions of superficial layers of the superior colliculus (SC) show partial sparing of this response, particularly for targets in the central visual field. In this study, we sought to determine whether these spared orienting abilities are mediated by aberrant retinal projections to the remaining intermediate layers of the SC, or whether visual cortex (VC) mechanisms or alternative behavioral strategies are responsible. Neonatal golden hamsters received either bilateral heat lesions of the SC (rlSC), or a heat lesion of the right SC and enucleation of the right eye (rSCrE). This latter procedure causes axons from the left eye to recross the tectal midline and terminate in the wrong (left) SC (Schneider 1973). As adults, both groups of hamsters were extremely deficient in visually guided approach to stationary targets, although rlSC-lesioned hamsters showed some sparing for central field targets and rSCrE-lesioned hamsters often made wrong-direction turns for targets in the left peripheral field. We then subjected both groups of neonatally lesioned hamsters to bilateral aspiration lesions of the VC. Retesting showed no change in visual orienting behavior as a result of the cortical lesions. Labeling of the optic tract with horseradish peroxidase (HRP) revealed abundant aberrant retinal projections to remaining intermediate layers of the SC and thalamic nucleus lateralis posterior (LP), as well as supernormal innervation of pretectal nuclei, the dorsal terminal nucleus of the accessory optic tract, and the ventral nucleus of the lateral geniculate body (LGv). We conclude that the spared visual orienting capabilities of hamsters with rlSC and rSCrE lesions are mediated by the aberrant midbrain projections, and that cortical mechanisms are not involved in spared visual orienting functions following these neonatal lesions.     

On the development of the pyramidal tract in the rat

Summary An anterograde tracer study has been made of the developing corticospinal tract (CST) in the rat using wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP). Analysis of normal Rager stained material revealed that corticospinal axons reach upper cervical spinal cord levels at the day of birth (PO). Postnatal rats ranging in age from one (P1) to fourteen (P14) days received multiple WGA-HRP injections into the cortex of their left hemisphere and were allowed to survive for 24 h. The first labeled CST fibers caudally extend into the third thoracic spinal cord segment at P1; into the eighth thoracic segment at P3; into the first or second lumbar segment at P7 and into the second to third sacral segment at Pg. Thus the outgrowth of the leading pioneer fibers of the CST is completed at P9 but later developing axons are continuously added even beyond P9. Quantitative analysis of the amount of label along the length of the outgrowing CST revealed a characteristic pattern of labeling varying with age. The most striking features of that pattern are: (1) the formation of two standing peaks at the level of the cervical and lumbar enlargements respectively and (2) the transient presence of a smaller running peak which moves caudally with the front of the outgrowing bundle. The standing peaks are ascribed to the branching of the axon terminals at both intumescences, whereas the running peak probably arises by the accumulation of tracer within the growth cones at the tips of the outgrowing CST axons. Factors such as the number of axons, the varying axon diameters, the branching collaterals, the presence of varicosities, the transport rate of the tracer, the uptake of the tracer at the injection site, which possibly may affect the amount of label present in both the entire bundle and in the individual axons are discussed. Current research is focused upon an analysis of the relation between the site of injection within the cortex and the pattern of labeling of the CST. A delay of two days was found between the arrival of the CST axons at a particular spinal cord level and their outgrowth into the adjacent spinal gray. However, combined HRP and electronmicroscopic experiments are necessary to determine the factors behind the maturation of the CST as well as the maturation of the spinal gray.     

The reciprocal connections of the suprageniculate nucleus and the superior colliculus in the rat

Reciprocally bilateral connections between the superior colliculus and the suprageniculate nucleus have been studied in the rat, using the anterograde and retrograde transport techniques of HRP. In those cases where the HRP deposit was restricted to the superficial layers of the colliculus, anterogradely labeled fibers and retrogradely labeled neurons were observed in the ipsilateral suprageniculate nucleus. However, upon HRP injection extended into the intermediate layers of the colliculus, the number of labeled fibers and neurons was not only increased ipsilaterally but were also observed in the contralateral suprageniculate nucleus. The density of the labeled fibers and the number of labeled neurons was always greater in the ipsilateral side. These results show that the suprageniculate nucleus and the superior colliculus are connected reciprocally and bilaterally, with an ipsilateral dominance.     

The projection from the superior colliculus to the lateral reticular nucleus in the cat as studied with retrograde transport of WGA-HRP

Summary Medium-sized and large superior collicular neurons were retrogradely labelled after small ejections of the wheat germ agglutinin-horseradish peroxidase complex in the lateral reticular nucleus of the feline medulla. The projection from the superior colliculus to the lateral reticular nucleus is bilateral with a contralateral predominance. It originates mainly from the intermediate, but also from the deep gray layer of the superior colliculus. Our observations provide evidence that the lateral reticular nucleus is an important target of tectal efferents. The findings are discussed in relation to the organization of other fiber connections of the superior colliculus.     

Effects on visual search of lesions of the superior colliculus in infant or adult rats

Summary The superior colliculus was removed from rats at either one or five days of age or in maturity. Four months later they were tested on two versions of a visual search task. Experiment 1 required animals to retrieve food pellets concealed in a depression in the top of identical narrow pillars arranged in an arena. Rats with lesions of the superior colliculus, regardless of the age at operation, showed a large number of return errors compared with sham-operated controls. Return errors were defined as occasions on which the animal returned to pillars that had previously been visited on that trial, before every pillar had been visited at least once. Experiment 2 compared the ability of infantand adult-operated animals to detect and locate a single, baited white pillar in an array of black ones. There were no group differences in response latencies to targets presented in the rostral visual field (within 40° of the midline). However, animals operated on in adulthood or at 5 days of age were slower than both sham-operated animals and animals operated on at one day of age in their responses to more peripheral targets. The latter two groups were indistinguishable.     

Developmental changes in NMDA receptor-mediated visual activity in the rat superior colliculus, and the effect of dark rearing

N-methyl-D-aspartate (NMDA) receptor-mediated activity is considered important for experience-dependent plasticity in the developing visual system. We investigated the influence of age and experience on the role of NMDA receptors in the visual transmission in the superficial grey layer of the superior colliculus (SGS) of the superior colliculus, where, in the adult, NMDA receptors mediate a substantial part of the visual response. In normally reared (postnatal day 14, P14, to adult) rats, visual responses were challenged with NMDA receptor-selective iontophoretic applications of the antagonist D-2-amino-5-phosphonovalerate (AP5). After eye opening (at P14), there was a significant increase in the number of neurones whose visual responses were reduced during AP5 ejection, which peaked at P22 (85%; n = 21), and then declined to adult levels (66%; n = 47) at P25. The mean reduction of the response (from control levels) by AP5 was similar at all ages (approximately 40%). Dark rearing had striking effects on the role of NMDA receptors in visual transmission, especially when comparisons were made between age-matched subjects greater than P25. In these subjects, AP5 ejection reduced the visual responses of all neurones studied. In addition, AP5 ejection caused a significantly larger reduction of visual responses in dark-reared rats (mean reduction 62 ± 4; n = 29) compared with age-matched controls (mean reduction 44 ± 8; n = 23). The D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced the visual responses of every neurone studied and there were no age- or experience-dependent effects. We conclude that NMDA receptors, but not AMPA receptors, assume greater importance for visual transmission in the SGS of dark-reared rats. Received: 2 May 1997 / Accepted: 19 November 1997     

Cytoarchitectonic coincidence with the discontinuous connectional pattern in the deep layers of the superior colliculus in the rat

The aims of the present study are to demonstrate cytoarchitectonically columnar structures in the deep layers of the rat's superior colliculus, and to show experimentally the existence of a clear correlation between the cytoarchitectonically defined columnar structures and the discontinuous patterns of the tectal connections in the deep layers. Injections of horseradish peroxidase conjugated to wheat germ agglutinin (HRP-WGA) into the prefrontal cortex produced orthograde labeling in the columnar structures in the deep layers of the superior colliculus, while HRP-WGA injections into the somatic sensory cortex resulted in orthograde labeling in the areas outside the columnar structures, so that the distribution patterns of terminals from these two different cortical areas are complementary in the deep layers. Cells of origin of the tectal efferents are also differentiated in terms of the columnar structures; HRP-WGA injections into the dorsal medial nucleus of the thalamus yielded retrograde labeling of spindle-cells within the columns, whereas the injections into the trigeminal sensory nuclei produced retrograde labeling of polygonal cells in the areas outside of the columns. These results suggest that as in the dorsoventral laminar coincidence with the tectal connections, there is a well organized mediolateral registration of the tectal connections with the cytoarchitectonically defined cell arrangement in the deep layers of the superior colliculus.     

Lesion-induced plasticity of central neurons: sprouting of single fibres in the rat hippocampus after unilateral entorhinal cortex lesion

In response to a central nervous system trauma surviving neurons reorganize their connections and form new synapses that replace those lost by the lesion. A well established in vivo system for the analysis of this lesion-induced plasticity is the reorganization of the fascia dentata following unilateral entorhinal cortex lesions in rats. After general considerations of neuronal reorganization following a central nervous system trauma, this review focuses on the sprouting of single fibres in the rat hippocampus after entorhinal lesion and the molecular factors which may regulate this process. First, the connectivity of the fascia dentata in control animals is reviewed and previously unknown commissural fibers to the outer molecular layer and entorhinal fibres to the inner molecular layer are characterized. Second, sprouting of commissural and crossed entorhinal fibres after entorhinal cortex lesion is described. Single fibres sprout by forming additional collaterals, axonal extensions, boutons, and tangle-like axon formations. It is pointed out that the sprouting after entorhinal lesion mainly involves unlesioned fibre systems terminating within the layer of fibre degeneration and is therefore layer-specific. Third, molecular changes associated with axonal growth and synapse formation are considered. In this context, the role of adhesion molecules, glial cells, and neurotrophic factors for the sprouting process are discussed. Finally, an involvement of sprouting processes in the formation of neuritic plaques in Alzheimer's disease is reviewed and discussed with regard to the axonal tangle-like formations observed after entorhinal cortex lesion.