The therapeutic effect and mechanism of Chinese medicine Xuan-Yun-Ding on posterior circulation ischemia with vertigo in a rabbit model.

The aim of research is to unveil the mechanisms of the beneficial effects of XYD on PCIV in a rabbit model. 40 New Zealand white rabbits were randomly divided into 5 groups,including normal control group (NC), model control group (MC), low-dose of XYD group (LXYD), high-dose of XYD group (HXYD) and Yang-Xue-Qin-Nao group (YXQN). PCIV rabbit model was established by feeding high-fat diet companied with paravertebral sclerotherapy and rotation exercise. The general observation, step-down test, rheoencephalogram, blood tests, histopathological detection and the plasma concentration of the effective component of XYD were investigated. After pharmacological intervening, the step-down time, REG, PL, IPL, blood viscosity, the levels of blood lipids, CRGP were significantly improved. Moreover, the vertebral artery showed the reduced stenosis of arterial lumen and less proliferation of fibrous tissue in the arterial wall in the LXYD, HXYD and YXQN group. Based on the LC-MS detection, the blood concentrations of puerarin in the LXYD and HXYD group were significantly increased after pharmacological intervening. XYD could ameliorate the symptoms of vertigo, Qi-deficiency and blood stasis in PCIV rabbits via effectively regulating the levels of blood lipids and vasoactive substances, decreasing blood viscosity, increasing CBF and protecting vestibular function.

Central Vestibular Tuning Arises from Patterned Convergence of Otolith Afferents.

As sensory information moves through the brain, higher-order areas exhibit more complex tuning than lower areas. Though models predict that complexity arises via convergent inputs from neurons with diverse response properties, in most vertebrate systems, convergence has only been inferred rather than tested directly. Here, we measure sensory computations in zebrafish vestibular neurons across multiple axes in vivo. We establish that whole-cell physiological recordings reveal tuning of individual vestibular afferent inputs and their postsynaptic targets. Strong, sparse synaptic inputs can be distinguished by their amplitudes, permitting analysis of afferent convergence in vivo. An independent approach, serial-section electron microscopy, supports the inferred connectivity. We find that afferents with similar or differing preferred directions converge on central vestibular neurons, conferring more simple or complex tuning, respectively. Together, these results provide a direct, quantifiable demonstration of feedforward input convergence in vivo.

Dynamics of glutamatergic synapses in the medial vestibular nucleus of the mouse.

During sinusoidal rotation or translation, primary vestibular afferents modulate their discharge rates at the frequency of motion, effectively transmitting frequency-modulated (FM) signals. This study indicates a possible role for excitatory synapses in the processing of FM signals by vestibular brainstem pathways. Inputs to medial vestibular neurons were activated with FM pulse trains, while inhibitory transmission was blocked. The relationship between the presynaptic pulse rate and the postsynaptic membrane potential was found to be linear within a range of pulse rates. Short-term plasticity was a factor contributing to sensitivity at higher modulating frequencies. The amount of low-pass filtering was correlated with excitatory postsynaptic potential (EPSP) shape, which affected temporal summation during the train. Although the NMDA component of glutamatergic transmission affected EPSP shape, it made only a minor contribution to the dynamics of synaptic transmission. Most responses showed low-pass filtering over the entire 1-16 Hz range. Overall, excitatory synapses in the medial vestibular nucleus contribute a low-pass filter to central vestibular processing and complement the high-pass filtering that is introduced both by peripheral vestibular dynamics and by the intrinsic dynamics of secondary vestibular neurons.

Connections of the superior vestibular nucleus with the oculomotor and red nuclei in the rat: an electron microscopic study.

Phaseolus vulgaris leucoagglutinin (PHA-L) was injected into the individual vestibular nuclei of the rat to study their efferent connections. One of the major differences between the connections of these nuclei was found at the level of the mesencephalon: the eye-moving cranial nerve nuclei received the densest projection from the superior vestibular nucleus (SVN). In the present electron microscopic study, we have found that terminals of SVN origin established symmetric synaptic contacts in the oculomotor nucleus. More than two-thirds of PHA-L-labeled boutons terminated on dendrites, the rest of them established axosomatic contacts. Most of the labeled terminals were GABA-positive, supporting the results of previous physiological experiments, which showed inhibitory effects. In the mesencephalon, the other termination area was found in the red nucleus. The PHA-L-labeled boutons of SVN origin were in close contact with the perikarya and proximal dendrites of the magnocellular part of the red nucleus. The types of synaptic contacts and distribution of terminals of SVN origin were similar to those found in the oculomotor nucleus. Our results indicate that the SVN can modify the activity of the cerebellorubral and corticorubral pathways, exerting inhibitory action on the neurons of the red nucleus.

Mitochondrial ultrastructure and apoptotic protein expression in the vestibular nucleus complex following unilateral labyrinthectomy.

We hypothesized that peripheral vestibular disorders might affect mitochondria in the vestibular nucleus complex (VNC). We tested this using unilateral labyrinthectomy (UL) as a model for the effects of vestibular damage on the VNC and used Western blotting and electron microscopy to analyze mitochondria. In rats receiving UL we did not find any changes in mitochondrial ultrastructure in the medial vestibular nucleus following UL, and there was no change in the expression or activation of the apoptosis effector caspase-3 in the whole VNC following UL. However, we did detect a small but statistically significant upregulation of the anti-apoptotic protein Bcl-2 in the contralateral VNC at 10 h post-UL.

Developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei: role of group I metabotropic glutamate receptors.

The effects of high frequency stimulation (HFS) of the primary vestibular afferents on synaptic transmission in the ventral part of the medial vestibular nuclei (vMVN) were studied during postnatal development and compared with the changes in the expression of the group I metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5. During the first stages of development, HFS always induced a mGluR5- and GABAA-dependent long-term depression (LTD) which did not require NMDA receptor and mGluR1 activation. The probability of inducing LTD decreased progressively throughout the development and it was zero at about the end of the second postnatal week. Conversely, long-term potentiation (LTP) appeared at the beginning of the second week and its occurrence increased to reach the adult value at the end of the third week. Of interest, the sudden change in the LTP frequency occurred at the time of eye opening, about the end of the second postnatal week. LTP depended on NMDA receptor and mGluR1 activation. In parallel with the modifications in synaptic plasticity, we observed that the expression patterns and localizations of mGluR5 and mGluR1 in the medial vestibular nuclei (MVN) changed during postnatal development. At the earlier stages the mGluR1 expression was minimal, then increased progressively. In contrast, mGluR5 expression was initially high, then decreased. While mGluR1 was exclusively localized in neuronal compartments and concentrated at the postsynaptic sites at all stages observed, mGluR5 was found mainly in neuronal compartments at immature stages, then preferentially in glial compartments at mature stages. These results provide the first evidence for a progressive change from LTD to LTP accompanied by a distinct maturation expression of mGluR1 and mGluR5 during the development of the MVN.

L-citrulline immunostaining identifies nitric oxide production sites within neurons.

The cellular and subcellular localization of L-citrulline was analyzed in the adult rat brain and compared with that of traditional markers for the presence of nitric oxide synthase. Light, transmission electron, and confocal laser scanning microscopy were used to study tissue sections processed for immunocytochemistry employing a monoclonal antibody against L-citrulline or polyclonal anti-neuronal nitric oxide synthase sera, and double immunofluorescence to detect neuronal nitric oxide synthase and L-citrulline co-localization. The results demonstrate that the same CNS regions and cell types are labeled by neuronal nitric oxide synthase polyclonal antisera and L-citrulline monoclonal antibodies, using both immunocytochemistry and immunofluorescence. Short-term pretreatment with a nitric oxide synthase inhibitor reduces L-citrulline immunostaining, but does not affect neuronal nitric oxide synthase immunoreactivity. In the vestibular brainstem, double immunofluorescence studies show that many, but not all, neuronal nitric oxide synthase-positive cells co-express L-citrulline, and that local intracellular patches of intense L-citrulline accumulation are present in some neurons. Conversely, all L-citrulline-labeled neurons co-express neuronal nitric oxide synthase. Cells expressing neuronal nitric oxide synthase alone are interpreted as neurons with the potential to produce nitric oxide under other stimulus conditions, and the subcellular foci of enhanced L-citrulline staining are viewed as intracellular sites of nitric oxide production. This interpretation is supported by ultrastructural observations of subcellular foci with enhanced L-citrulline and/or neuronal nitric oxide synthase staining that are located primarily at postsynaptic densities and portions of the endoplasmic reticulum. We conclude that nitric oxide is produced and released at focal sites within neurons that are identifiable using L-citrulline as a marker.

Microgravity (STS-90 Neurolab-Mission) influences synapse formation in a vestibular nucleus of fish brain.

Synapse counting was undertaken by conventional electron microscopy in primary vestibular integration centers (i.e., Nucleus descendens, Nd, and Nucleus magnocellularis, Nm, of the brainstem Area octavolateralis) and in the diencephalic visual Nucleus corticalis (Nc) of spaceflown neonate swordtail fish Xiphophorus helleri as well as in 1 g control siblings. Spaceflight (16 days microgravity, STS-90 Neurolab-Mission) yielded an increase in synaptic contacts only within the vestibular Nd indicating that lack of input resulted in compensation processes. No effect of microgravity, however, was observed in the visual Nc and in the vestibular Nm which is situated in the close vicinity of the Nd. In contrast to the latter, the Nm does not receive exclusively vestibular input, but inputs from the lateral line as well, possibly providing sufficient input at microgravity.

Vestibular compensation after ganglionectomy: ultrastructural study of the tangential vestibular nucleus and behavioral study of the hatchling chick.

The tangential nucleus is a major part of the avian vestibular nuclear complex, and its principal cells are structurally distinctive neurons participating in the vestibuloocular and vestibulocollic reflexes. After unilateral peripheral vestibular lesion, a behavioral recovery of function defined as vestibular compensation is observed. Because sprouting and hypertrophy of synapses have been reported in other regions of immature animals after central nervous system injury, we investigated whether this also occurs in the vestibular nuclei during compensation. To test this hypothesis, unilateral vestibular ganglionectomy was performed on 4-6-day-old hatchlings and vestibular function was tested during the next 2 months. Degeneration and evidence for regeneration of synapses were studied in the tangential nucleus at 1, 3, 7, and 56 days after surgery. Spoon endings, large vestibular terminals on the principal somata, degenerated 1-3 days after surgery. However, the small synaptic terminals showed no significant change in the percentage or number covering the soma or in mean terminal lengths in the deafferented or contralateral tangential nucleus. Furthermore, there was no evidence of neuron death in the tangential nucleus. Vestibular compensation occurred in three stages: 0-3 days, when vestibular synapses degenerated and severe behavioral deficits were seen; 4-9 days, when primary vestibular fibers degenerated centrally and marked improvement in both the static and the dynamic symptoms were observed; and 10-56 days, when changes in neuronal morphology were not detected but the dynamic symptoms gradually improved. Accordingly, after unilateral vestibular ganglionectomy, vestibular compensation proceeded without ultrastructural evidence of sprouting or hypertrophy of axosomatic synapses in the hatchling tangential nucleus. This rapid behavioral recovery of function distinguishes the vestibular system from other sensory systems, which, in general, exhibit much less robust recovery after injury to their peripheral receptors.

Postsynaptic actin filaments at the giant mossy fiber-unipolar brush cell synapse.

The unipolar brush cell (UBC), a small interneuron occurring at high density in the granular layer of the mammalian vestibulocerebellum, receives a giant glutamatergic synapse from a single mossy fiber (MF) rosette, usually on a brush of dendritic branchlets. MF stimulation produces a current in the UBC several orders of magnitude greater in duration than at other glutamatergic synapses. We assumed that the cytoskeleton would have a special role in plasticity of the MF-UBC synapse. Neurofilaments and microtubules are enriched in the UBC somatodendritic compartment but are conspicuously absent in close proximity to the giant synapse, where standard electron microscopy reveals a granulo-flocculent material. Because osmium tetroxide fixation during sample preparation for standard electron microscopy destabilizes actin filaments, we hypothesized that this subsynaptic granulo-flocculent material is actin-based. After actin stabilization, we observed prominent, but loosely organized, bundles of microfilaments at the subsynaptic region of the MF-UBC synapse that linked the postsynaptic density with the cytoskeletal core of the dendritic branchlets. Confocal fluorescence microscopy and pre- and postembedding immunogold labeling with phalloidin and actin antibodies showed that these microfilaments consist of f-actin and contain little beta-actin. This extraordinary postsynaptic actin apparatus is ideally situated to form a dynamic framework for glutamate receptors and other postsynaptic molecules, and to mediate activity-dependent plastic rearrangements of the giant synapse.

Optical recording of membrane potential in dissociated mouse vestibular ganglion cells using a voltage-sensitive dye.

We investigated membrane electrophysiological features of dissociated vestibular ganglion neurons, using a voltage-sensitive dye and a multiple site optical imaging system. The neuronal nature of the cultured vestibular ganglion cells was confirmed by positive staining with the anti-neurofilament 200 kDa antibody, using immunocytochemical methods. Optical absorption of the dye which binds to the external surface of neuron membranes increased while the cells were depolarized during perfusion with 150 mM potassium solution. The relative ratio (deltaI/I) of optical absorption change was 0.23 +/- 0.08% (means +/- S.D., n = 16). These optical responses were wavelength dependent, therefore, the optical response apparently originated from the voltage-sensitive dye. Under our experimental conditions, photodynamic damage and pharmacological effects of the dye were either absent or insignificant. We therefore concluded that optical recording is a new, practical and non-invasive method to simultaneously monitor changes in membrane potential from cultured vestibular ganglion cells. Optical recording is expected to provide further insight into mechanisms of information processing by vestibular ganglion neurons.

Segment-specific branching patterns of single vestibulospinal tract axons arising from the lateral vestibular nucleus in the cat: A PHA-L tracing study.

The purpose of the present study was to detail the spinal cord (SC) trajectories and arborization patterns of vestibulospinal axons descending from the lateral vestibular nucleus (LVN). An anterograde neural tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L), was focally injected into the right-side LVN in 8 cats. Their subsequent survival times varied from 4 days to 12 weeks. The labeled axons were found mainly in the brainstem after 4-5 days and in successively more caudal spinal segments after longer survival times: i.e., in C1-T2 after 2-3 weeks, in C3-T11 after 6-7 weeks, and in T7-S1 after 10-12 weeks. The trajectories of 28 single, thick (diameter >/=2.4 microm) lateral vestibulospinal tract (LVST) axons were traced from serial transverse sections of the SC from C1-8 (n = 10), T1-9 (n = 11), and T11-L7 (n = 7). In the cervical segments, the LVST axons gave off collateral fibers, which terminated mainly in Rexed's laminae VII-VIII. The terminal-field patterns of these collaterals differed from one stem axon to another. In the thoracic segments, the terminal-field patterns from a given LVST axon were similar at each segmental level, i.e., a few main branches with or without short side branches. At the L3-5 midlumbar level, the collaterals usually arborized more extensively, such that their terminal fields occupied a much greater region of laminae VII-VIII. In contrast, at the L6-7 lower lumbar level, collaterals arising from thin axons (diameter <1.0 microm) tended to innervate, with even more extensive arborization, the medial part of the lamina VIII. These results revealed common and segment-specific collateral distribution patterns of LVST axons along the full extent of the spinal neuraxis.

Ultrastructural features of non-commissural GABAergic neurons in the medial vestibular nucleus of the monkey.

The ultrastructural characteristics of non-degenerating GABAergic neurons in rostrolateral medial vestibular nucleus were identified in monkeys following midline transection of vestibular commissural fibers. In the previous papers, we reported that most degenerated cells and terminals in this tissue were located in rostrolateral medial vestibular nucleus, and that many of these neurons were GABA-immunoreactive. In the present study, we examined the ultrastructural features of the remaining neuronal elements in this medial vestibular nucleus region, in order to identify and characterize the GABAergic cells that are not directly involved in the vestibular commissural pathway related to the velocity storage mechanism. Such cells are primarily small, with centrally-placed nuclei. Axosomatic synapses are concentrated on polar regions of the somata. The proximal dendrites of GABAergic cells are surrounded by boutons, although distal dendrites receive only occasional synaptic contacts. Two types of non-degenerated GABAergic boutons are distinguished. Type A terminals are large, with very densely-packed spherical synaptic vesicles and clusters of large, irregularly-shaped mitochondria with wide matrix spaces. Such boutons form symmetric synapses, primarily with small GABAergic and non-GABAergic dendrites. Type B terminals are smaller and contain a moderate density of round/pleomorphic vesicles, numerous small round or tubular mitochondria, cisterns and vacuoles. These boutons serve both pre- and postsynaptic roles in symmetric contacts with non-GABAergic axon terminals. On the basis of ultrastructural observations of immunostained tissue, we conclude that at least two types of GABAergic neurons are present in the rostrolateral portion of the monkey medial vestibular nucleus: neurons related to the velocity storage pathway, and a class of vestibular interneurons. A multiplicity of GABAergic bouton types are also observed, and categorized on the basis of subcellular morphology. We hypothesize that "Type A" boutons correspond to Purkinje cell afferents in rostrolateral medial vestibular nucleus, "Type B" terminals represent the axons of GABAergic medial vestibular nucleus interneurons, and "Type C" boutons take origin from vestibular commissural neurons of the velocity storage pathway.

Distribution of bulbospinal gamma-aminobutyric acid-synthesizing neurons of the ventral respiratory group of the rat.

Spinal respiratory motoneuron activity is controlled primarily by excitatory and inhibitory neurons in the medulla oblongata. To identify bulbospinal inhibitory neurons, immunohistochemistry for glutamic acid decarboxylase (GAD) was combined with retrograde labeling of projections to the C(4) ventral horn with Fluoro-Gold. GAD-immunoreactive bulbospinal neurons were located in the ventrolateral portion of the intermediate reticular nucleus, the ventral portion of the medial reticular nuclei, and the raphe and spinal vestibular nuclei. Small numbers of bulbospinal ventral respiratory group neurons were GAD immunoreactive. These neurons were distributed throughout the rostral ventral respiratory group and the Bötzinger complex. Surprisingly, low numbers of Bötzinger neurons, a population thought to be exclusively inhibitory, were GAD immunoreactive. These results suggest that the rostral ventral respiratory group and the Bötzinger complex both contain heterogeneous bulbospinal neuron populations, only some of which have gamma-aminobutyric acid (GABA)-mediated inhibitory control over phrenic motoneurons. Furthermore, the ventral respiratory group contained many GABAergic neurons that lacked bulbospinal projections.

Neuronal loss in human medial vestibular nucleus.

The data concerning the effects of age on the brainstem are inconsistent, and few works are devoted to the human vestibular nuclear complex. The medial vestibular nucleus (MVN) is the largest nucleus of the vestibular nuclear complex, and it seems to be related mainly to vestibular compensation and vestibulo-ocular reflexes. Eight human brainstems have been used in this work. The specimens were embedded in paraffin, sectioned, and stained by the formaldehyde-thionin technique. Neuron profiles were drawn with a camera lucida at x330. Abercrombie's method was used to estimate the total number of neurons. We used the test of Kolmogorov-Smirnov with the correction of Lilliefors to evaluate the fit of our data to a normal distribution, and a regression analysis was performed to determine if the variation of our data with age was statistically significant. The present study clearly shows that neuronal loss occurs with aging. The total number of neurons decreases with age, from 122,241 +/- 651 cells in a 35-year-old individual to 75,915 +/- 453 cells in an 89-year-old individual. Neuron loss was significant in the caudal and intermediate thirds of the nucleus, whereas the changes in the rostral third were not significant. The nuclear diameter of surviving neurons decreased significantly with age. There is a neuron loss in the MVN that seems to be age-related. It could help explain why elderly people find it hard to compensate for unilateral vestibular deficits. The preservation of neurons in the rostral third could be related to the fact that this area primarily innervates the oculolmotor nuclei; these latter neurons do not decrease in number in other species studied.

Development of the human lateral vestibular nucleus: a morphometric evaluation.

The development of the human lateral vestibular nucleus was studied on serial sections of the brain of 8 fetuses and neonates at 12-40 weeks of gestation, an infant at 2 months of age and an adult of 63 years using a microscope with a drawing tube and an image-analysing computer system. A morphometric analysis revealed that the lateral vestibular nucleus, whose neurons were distinguished from glia after 16 weeks of gestation, divided cytoarchitectonically into the medial and the lateral subnuclei at 21 weeks of gestation onwards, and showed the moderate development in terms of the columnar length and volume, neuronal size and neuropil.

Morphological evidence for local microcircuits in rat vestibular maculae.

Previous studies suggested that intramacular, unmyelinated segments of vestibular afferent nerve fibers and their large afferent endings (calyces) on type I hair cells branch. Many of the branches (processes) contain vesicles and are presynaptic to type II hair cells, other processes, intramacular nerve fibers, and calyces. This study used serial section transmission electron microscopy and three-dimensional reconstruction methods to document the origins and distributions of presynaptic processes of afferents in the medial part of the adult rat utricular macula. The ultrastructural research focused on presynaptic processes whose origin and termination could be observed in a single micrograph. Results showed that calyces had 1) vesiculated, spine-like processes that invaginated type I cells and 2) other, elongate processes that ended on type II cells pre- as well as postsynaptically. Intramacular, unmyelinated segments of afferent nerve fibers gave origin to branches that were presynaptic to type II cells, calyces, calyceal processes, and other nerve fibers in the macula. Synapses with type II cells occurred opposite subsynaptic cisternae (C synapses); all other synapses were asymmetric. Vesicles were pleomorphic but were differentially distributed according to process origin. Small, clear-centered vesicles, approximately 40-60 nm in diameter, predominated in processes originating from afferent nerve fibers and basal parts of calyces. Larger vesicles approximately 70-120 nm in diameter having approximately 40-80 nm electron-opaque cores were dominant in processes originating from the necks of calyces. Results are interpreted to indicate the existence of a complex system of intrinsic feedforward (postsynaptic)-feedback (presynaptic) connections in a network of direct and local microcircuits. The morphological findings support the concept that maculae dynamically preprocess linear acceleratory information before its transmission to the central nervous system.

Distribution pattern and ultrastructural localization of Rxt1, an orphan Na+/Cl(-)-dependent transporter, in the central nervous system of rats and mice.

The cellular and subcellular localization of Rxt1 protein, an orphan Na+/Cl(-)-dependent transporter, was investigated in the central nervous system of rats and mice, with rabbit polyclonal antibodies specifically directed against its C-terminal region. At the light microscope level, the distribution of Rxt1, visualized by the immunoperoxidase method, was found to be similar in rats and mice. Labelled elements were present in numerous gray matter regions of the central nervous system, from the olfactory bulb to the spinal cord. In all labelled regions, immunoreactivity was confined to the neuropil where both a diffuse labelling of low intensity and an intense punctate staining were noted. To further identify the nature of the cellular elements bearing the punctate staining, possible changes in this labelling pattern were investigated: (i) in deep cerebellar nuclei and lateral vestibular nucleus of the Lurcher mutant mouse, in which all cerebellar Purkinje cells are missing and (ii) in the rat cervical spinal cord, 10 days after multiple resections of dorsal roots. The vast majority of the punctate structures, delineating the neuronal perikaryal and stem dendritic contours, had disappeared in the mutant mouse, providing evidence that they belong to Purkinje cell axon terminals. In rhizotomized rats, the intense labelling in laminae I and III had disappeared, demonstrating that it occurred in subclasses of axonal projections of primary afferent fibres. These results strongly suggest that Rxt1 is present in presynaptic axon terminals. The electron microscopic study was carried out in the hippocampus, cerebellum and lateral vestibular nucleus of control mice, where Rxt1-labelled punctate structures were found to be abundant. Immunostaining was confined to axon terminals, particularly in hippocampal and cerebellar mossy fibres and in Purkinje cell axonal terminations of the cerebellar deep nuclei and lateral vestibular nucleus. In the cerebellar cortex, axon terminals belonging to inhibitory local circuit neurons (basket and Golgi cells), were free of labelling. The observations reported in this study have shown that: (1) The Rxt1 transporter is neuron-specific, and is expressed by only some classes or even subclasses of neuronal systems. (2) This transporter can be encountered in excitatory axons using glutamate as neurotransmitter (hippocampal and cerebellar mossy fibres: primary afferent fibres), as well as in inhibitory axons known by their GABAergic nature (Purkinje cell axon terminals) where it might be involved in the re-uptake process of one or several molecules released from corresponding terminals.

Age-related appearance of dystrophic axon terminals in cerebellar and vestibular nuclei of Mongolian gerbils.

In the brains of 360-day-old Mongolian gerbils, numerous swellings immunoreactive to anti-neurofilament antibody were observed in cerebellar and vestibular nuclei. The number of these swellings was the same in two gerbil strains with different susceptibility to spontaneous motor seizures by various stimuli, but much more numerous in gerbils as compared with the 360-day-old Slc:Wistar rats. Such swellings were only occasionally found before 60 days of age in gerbils, but they increased in number about fivefold from 60 to 180 days of age and about quadruple from 180 to 360 days of age. Electron microscopic observation showed that these swellings were dystrophic axon terminals (DATs) whose cytoplasms were occupied with large bundles of neurofilaments, numerous vesicular structures containing membranous and/or granular materials, and many rod-shaped mitochondria. Additionally, other types of DATs displaying degenerative changes of cytoplasmic organelles were observed. ACPase cytochemistry showed that the vesicular structures in the DATs contained ACPase and released it into the cytoplasm.