Characterization of input synapses on intracellularly stained neurons in hippocampal slices: an HRP/EM study

Summary This study describes the fine structure of input synapses on identified neurons in slices of the guinea pig hippocampus. For morphological identification, granule cells of the fascia dentata and pyramidal neurons of regio inferior of the hippocampus were impaled and intracellularly stained with horse-radish peroxidase (HRP). Input synapses on the HRP-stained neurons were identified in the electron microscope by the location of the synapses in inner or outer zones of the dentate molecular layer, as in the case of the synaptic contacts on injected granule cells, or by unique fine structural characteristics, as in the case of the giant mossy fiber boutons on CA3 pyramidal cells. As in tissue fixed in situ by transcardial perfusion, a large number of terminals arising from the different afferents in inner and outer zones of the dentate molecular layer were well preserved and formed synaptic contacts with small spines, large complex spines, and dendritic shafts of the HRP-filled granule cells. Mossy fiber synapses on the stained CA3 neurons were densely filled with clear vesicles, contained a few dense-core vesicles, and formed synaptic contacts with large spines or excrescences. Occasionally electrondense degenerating boutons were also found impinging on the stained dendrites and spines. The significance of the present findings for electrophysiological and pharmacological studies on brain slices is discussed.     

The effects of chronic glucocorticoid exposure on dendritic length, synapse numbers and glial volume in animal models: Implications for hippocampal volume reductions in depression

Glucocorticoids (GCs) are hormones secreted by the adrenal glands as an endocrine response to stress. Although the main purpose of GCs is to restore homeostasis when acutely elevated, animal studies indicate that chronic exposure to these hormones can cause damage to the hippocampus. This is indicated by reductions in hippocampal volume, and changes in neuronal morphology (i.e., decreases in dendritic length and number of dendritic branch points) and ultrastructure (e.g., smaller synapse number). Smaller hippocampal volume has been also reported in humans diagnosed with major depressive disorder or Cushing's disorder, conditions in which GCs are endogenously and chronically elevated. Although a number of studies considered neuron loss as the major factor contributing to the volume reduction, recent findings indicated that this is not the case. Instead, alterations in dendritic, synaptic and glial processes have been reported. The focus of this paper is to review the GC effects on the cell number, dendritic morphology and synapses in an effort to better understand how these changes may contribute to reductions in hippocampal volume. Taken together, the data from animal models suggest that hippocampal volumetric reductions represent volume loss in the neuropil, which, in turn, under-represent much larger losses of dendrites and synapses.     

基于类Hopfield脉冲神经网络模型由突触缺失导致海马CA3区联想记忆功能障碍的建模仿真研究

目的 建立1个类Hopfield脉冲神经网络模型,仿真海马中突触缺失导致的其联想记忆功能障碍.方法 根据海马CA3区的解剖结构,建立1个具有自联想记忆功能和异联想记忆功能的3层类Hopfield脉冲神经网络模型,并用Matlab对网络的2种联想记忆功能进行仿真,并根据Ruppin的‘突触缺失＇理论,仿真了由突触缺失导致的CA3区联想记忆功能障碍.结果 随着突触缺失水平的增加,网络的2种联想记忆能力均下降.结论 海马CA3区神经元突触缺失不仅导致其自联想记忆能力下降,也会导致其异联想记忆能力下降.     

Changes in the total number of dentate granule cells in juvenile and adult rats: A correlated volumetric and 3H-thymidine autoradiographic study

Summary The total number of granule cells in the dentate gyrus was estimated in 17 male rats, four each aged 30, 120, and 200 days, and five aged 365 days. There is a substantial 35–43% linear increase between 1 month and 1 year. Two parameters of the granular layer are involved in the numerical change. First, total granular layer volume grows linearly with age. Second, average volume of a single granule cell nucleus in the ventral dentate gyrus decreases with age. Older rats tend to have a larger granular layer filled with more and smaller cells. In another group of 21 male rats, ³H-thymidine injections were given on four consecutive days during juvenile (30–33, n = 6) and adult life (60–63, n = 5; 120–123, n = 6; 180–183, n = 4). All animals survived to 200 days of age. The proportion of labeled mature granule cells and labeled presumptive granule cell precursors were determined in anatomically-matched slices. With older ages at injection, there is a decline in labeled mature granule cells and a concurrent increase in labeled precursors. These data are compatible with the constant level of granule cell increase determined volumetrically. Most of the late granule cells originate nearly simultaneously along the base of the main bulk of the granular layer; very few are found in the dorsal tip (septal extreme) and ventral tip (temporal extreme). This study is the first demonstration of a net numerical gain in a neuronal population during adulthood in the mammalian brain. Since the granule cells play a pivotal role in hippocampal function, these data suggest that their influence grows with age.Supported by the National Science Foundation (Grant No. BNS 79-21303)     

Unambiguous representation of overlapping serial events in the rat hippocampal formation

The hippocampal formation is suggested to be crucial in unambiguous representation of overlapping temporal sequences in episodic memory. We hypothesized that, if this was true, the hippocampal formation neurons would differentially respond to the same elements even in different temporal sequences. The present study was designed to investigate hippocampal formation CA1 neuronal activity of rats during performance of a conditional delayed stimulus-response association task in which three stimuli were conditionally and serially presented with a delay. In the task, the pairs of the second and third stimuli were overlapped across the trials, but separated by the preceding first stimuli. Conditioned tones coming from one of three possible directions were followed, after a short delay, by one of three pairs of reinforcement series. The pairs consisted of air puff (aversive sensory stimuli) and tube protrusion (which allowed licking sucrose behavior) in the following combinations: air puff-tube protrusion, tube protrusion-tube protrusion and tube protrusion-air puff. The pairs were interposed by a 2 s delay. The three conditioned tone directions were associated with these three pairs in a one-to-one correspondence, and its association was conditional to three possible conditioned tone frequencies (300, 530, and 1,200 Hz). The responses of 107 neurons to the air puff and tube protrusion were analyzed by two-way ANOVA (task condition x reinforcement situation). Of 42 air puff-responsive and 64 tube protrusion-responsive neurons, 36 and 53 displayed significant main effects and/or significant interaction, respectively. Furthermore, neural responses during the delay periods were dependent on the task conditions. The results indicated that the majority of the hippocampal formation neurons showed task condition- and/or reinforcement situation-dependent responses, suggesting a crucial role of the hippocampal formation in representation of overlapping serial events in episodic memory.     

Ontogeny of the dopamine D2 receptor mRNA expressing cells in the human hippocampal formation and temporal neocortex

The study details the cellular expression of the dopamine D₂ receptor mRNA in the human temporal lobe during prenatal development. At 13 embryonic weeks (E13) D₂ mRNA was widely expressed in the temporal lobe. At this time point in the dentate gyrus D₂ mRNA positive cells first appeared at the outer border of the granular layer and their number increased with development. The CA1 exhibited the highest level of D₂ mRNA expression. By E19–25 the hippocampal formation underwent rapid morphological maturation. D₂ mRNA expression became more uniform and dense in the ammonic subfield. At all ages the subiculum appeared more mature morphologically but less intensely stained for D₂ mRNA than the ammonic fields. In the entorhinal cortex D₂ mRNA expression was most conspicuous in the future layer II at all ages. In the temporal neocortex D₂ mRNA-positive cells were detected in the subplate and cortical plate. Differentiation of the cortical plate was accompanied by concentration of D₂ mRNA-positive cells in layer V. The most conspicuous cells expressing D₂ mRNA were found in the marginal zone of all regions and resembled Cajal–Retzius cells in morphology and location. Density of putative Cajal–Retzius cells expressing D₂ mRNA decreased with development. They all but disappeared from the hippocampal areas by mid gestation, but in the temporal neocortex occasional cells were seen even at term. Early and widespread but region and cell type specific expression of D₂ receptor mRNA suggests an important role of this DA receptor subtype in prenatal development of the human temporal lobe.     

Impact of N-tau on adult hippocampal neurogenesis,anxiety, and memory

Different pathological tau species are involved in memory loss in Alzheimer's disease, the most common cause of dementia among older people. However, little is known about how tau pathology directly affects adult hippocampal neurogenesis, a unique form of structural plasticity implicated in hippocampus-dependent spatial learning and mood-related behavior. To this aim, we generated a transgenic mouse model conditionally expressing a pathological tau fragment (26–230 aa of the longest human tau isoform, or N-tau) in nestin-positive stem/progenitor cells. We found that N-tau reduced the proliferation of progenitor cells in the adult dentate gyrus, reduced cell survival and increased cell death by a caspase-3–independent mechanism, and recruited microglia. Although the number of terminally differentiated neurons was reduced, these showed an increased dendritic arborization and spine density. This resulted in an increase of anxiety-related behavior and an impairment of episodic-like memory, whereas less complex forms of spatial learning remained unaltered. Understanding how pathological tau species directly affect neurogenesis is important for developing potential therapeutic strategies to direct neurogenic instructive cues for hippocampal function repair.     

Effects of changes in extracellular potassium,magnesium and calcium concentration on synaptic transmission in area CA1 and the dentate gyrus of rat hippocampal slices

The dependence of stimulus-induced synaptic potentials on changes of extracellular ionic concentrations of potassium ([K⁺]_o 3, 5, 8 mM), magnesium ([Mg²⁺]_o 2, 4, 8 mM) and calcium [Ca²⁺]_o (2 mM and continuous lowering by washing with Ca²⁺-free solutions) was investigated in area CA1 and dentate gyrus of rat hippocampal slices. Field potentials (fps), [K⁺]_o and [Ca²⁺]_o were measured with double-barreled ion selective/reference microelectrodes. Paired pulse stimulation (interval 50-ms) was applied either to the lateral perforant path or to the Schaffer collaterals. Elevation of [K⁺]_o from 5 to 8 mM and of [Mg²⁺]_o from 2 to 8 mM depressed the rise of excitatory postsynaptic potentials, as well as the amplitude of population spikes. With elevation of [K⁺]_o, the effect was stronger in the dentate gyrus, while with elevation of [Mg²⁺]_o, the reduction was more pronounced in area CA1. During washout of Ca²⁺, synaptic potentials became reduced and finally depressed. The [Ca²⁺]_o at which synaptic transmission was blocked increased with higher [Mg²⁺]_o and decreased with a change of [K⁺]_o from 3 to 5 mM, whereas with an elevation of [K⁺]_o from 5 to 8 mM, it rose in area CA1 but was reduced in dentate gyrus. All ionic changes also affected frequency habituation and potentiation in paired pulse experimentes. In dentate gyrus, frequency habituation was reversed to frequency potentiation with moderate lowering of [Ca²⁺]_o and with elevation of [Mg²⁺]_o and [K⁺]_o. In contrast, in area CA1 frequency potentiation was reduced upon elevation of [K⁺]_o.     

低氧预适应对小鼠海马神经元中TSC1表达的影响

目的:在体视显微镜下分割ICR小鼠海马CA1区和CA3区,研究结节性硬化症因子1(TSC1)在小鼠海马低氧中的神经保护作用。方法:ICR小鼠分为对照组(control)、低氧对照组(hypoxia)及低氧预适应组(HPC),在体视显微镜下观察海马形态并分割CA1区和CA3区;采用real time RT-PCR和Western Blot的方法分别检测小鼠海马组织TSC1 mRNA和蛋白的表达;采用免疫荧光检测小鼠海马组织TSC1荧光强度。结果:大脑冠状切片清晰显示出海马CA1区、CA3区和DG区; CA1区TSC1 mRNA在低氧组降低而在低氧预适应组增高;Western Blot和组织免疫荧光显示:与对照组相比,低氧预适应组CA1区TSC1表达增加;而CA3区TSC1在低氧组和低氧预适应组均增加。结论:TSC1的差异性表达可能提示TSC1可能参与了低氧预适应对低氧敏感的CA1区神经细胞的保护。     

17beta-Estradiol potentiates field excitatory postsynaptic potentials within each subfield of the hippocampus with greatest potentiation of the associational/commissural afferents of CA3

We sought to determine the impact of 17beta-estradiol throughout the hippocampal trisynaptic pathway and to investigate the afferent fiber systems within CA1 and CA3 in detail. To achieve this objective, we utilized multielectrode arrays to simultaneously record the field excitatory postsynaptic potentials from the CA1, dentate gyrus, and CA3 of rat hippocampal slices in the presence or absence of 100 pM 17beta-estradiol. We confirmed our earlier findings in CA1, where 17beta-estradiol significantly increased field excitatory postsynaptic potentials amplitude (20%+/-3%) and slope (22%+/-7%). 17beta-Estradiol significantly potentiated the field excitatory postsynaptic potentials in dentate gyrus, amplitude (15%+/-4%) and slope (17%+/-5), and in CA3, amplitude (15%+/-4%) and slope (19%+/-5%). Using a high-density multielectrode array, we sought to determine the source of potentiation in CA1 and CA3 by determining the impact of 17beta-estradiol on the apical afferents and the basal afferents within CA1 and on the mossy fibers and the associational/commissural fibers within CA3. In CA1, 17beta-estradiol induced a modest increase in the amplitude (7%+/-2%) and slope (9%+/-3%) following apical stimulation with similar magnitude of increase following basal stimulation amplitude (10%+/-2%) and slope (12%+/-3%). In CA3, 17beta-estradiol augmented the mossy fiber amplitude (15%+/-3%) and slope (18%+/-6%) and the associational/commissural fiber amplitude (31%+/-13%) and slope (40%+/-15%). These results indicate that 17beta-estradiol potentiated synaptic transmission in each subfield of the hippocampal slice, with the greatest magnitude of potentiation at the associational/commissural fibers in CA3. 17beta-Estradiol regulation of CA3 responses provides a novel site of 17beta-estradiol action that corresponds to the density of estrogen receptors within the hippocampus. The implications of 17beta-estradiol potentiation of the field potential in each of the hippocampal subfields and in particular CA3 associational/commissural fibers for memory function and clinical assessment are discussed.     

A study of glial cell proliferation in the molecular layer of the dentate gyrus of the rat following interruption of the ventral hippocampal commissure

Summary The proliferation of glial cells in the molecular layer of the dentate gyrus in response to lesions of the ventral hippocampal commissure, has been studied autoradiographically following intraventricular injections of ³H-thymidine. Within 24h of commissurotomy there is an appreciable increase in the number of labeled cells throughout the molecular layer which reaches its peak at approximately 36h. This generalized glial hyperplasia persists for at least 5–6 weeks and there does not appear to be a secondary re-distribution of the newly-generated glial cells as has been reported after entorhinal lesions (Gall et al., 1979). In semi-thin plastic sections most of the proliferating cells more closely resemble the medium-shade oligodendrocytes of Ling et al. (1973) than typical microglia; the reactive astrocytes do not appear to participate in the glial proliferation.This work was supported in part by grants NS-10943 from the NINCDS and DA-00259 from ADAMAH, and was carried out while C.A. was on leave of absence from the Department of Morphology, Autonoma University School of Medicine, Madrid, and was in receipt of a Fogarty International Fellowship (1F05 TWO 2580)     

Direct visualization of glucocorticoid receptor positive cells in the hippocampal regions using green fluorescent protein transgenic mice

The hippocampal formation is a plastic brain structure important for certain types of learning and memory, and also vulnerable to the effects of stress and trauma. Since hippocampal neurons express high levels of corticosteroid receptor, the morphological changes, including alterations in the size of soma, and the length and number of neurites and spines, in response to glucocorticoids released as a result of stress are intriguing. In order to highlight the morphology of neurons that express glucocorticoid receptor (GR), we have generated a transgenic mouse line expressing green fluorescent protein (GFP) under the control of the GR promoter. We found strong green fluorescence in the pyramidal cell layer of the CA1 and CA2 regions and the granule cell layer of the dentate gyrus of the hippocampus in brain sections of the transgenic mice. GFP fluorescence was observed not only in somas, but also in neurites including both dendrites and axons. In dissociated culture, we also observed GFP fluorescence in the soma, neurites including both dendrites and axons, and dendritic spines. Microtubule-associated protein 2 immunopositive pyramidal-shaped neurons clearly showed two different populations, GFP positive and GFP negative neurons. These results indicate that this transgenic mouse line should be useful for live imaging of neuronal structure in animals as well as GR-positive cultured cells using GFP as a specific indicator.     

Postnatal development of the light and electron microscopic features of basket cells in the hippocampal dentate gyrus of the rat

Summary Light and electron microscopic preparations were used to analyze the postnatal development of the basket cells of the rat dentate gyrus. The basket cells, located at the hilar border, were recognized in 2-day-old rats in Golgi preparations, where they displayed immature dendrites and a small axon arbor in the granule cell layer. At 5 days, the basket cells were found to have a large perikaryal cytoplasm, a round nucleus, an axon that forms symmetric synapses with granule cells, and dendrites and somata that are contacted by other axon terminals. The 10-day basket cells display more mature features, such as Nissl bodies and well-developed Golgi complexes. The basket cells from 16-day-old rats are mature in terms of their ultrastructural features, in that the nuclei are highly indented and display intranuclear rods or sheets, the perikaryal cytoplasm is packed with organelles, and the axon has developed an extensive arborization with the somata and dendrites of granule cells at the border with the molecular layer. This arborization will continue to expand as more granule cells are generated and added to the hilar border. These data correlate well with the immunocytochemical and biochemical development of GABAergic neurons in the dentate gyrus. Furthermore, the maturation of the structure of basket cells appears to precede the appearance of adult-like electrical activity in the hippocampus.     

Characterization of the cortical laser-Doppler flow and hippocampal degenerative patterns after global cerebral ischaemia in the goat

 Large-animal models offer several advantages in the study of cerebral ischaemia: easier control of physiological variables, easier neuropathological evaluation, etc. In the present study we have taken advantage of the unique cerebrovascular anatomy of the goat to reproduce a model of reversible, incomplete, global cerebral ischaemia in a large-sized animal species, in which the effects of successive manoeuvres to stop and re-start cerebral blood flow can be recorded continuously. Early cortical laser-Doppler flow response (up to 2 h) and delayed neuronal degeneration (7 days) in the hippocampal CA1 subfield have been analysed in goats undergoing 5, 10 or 20 min of transient, global cerebral ischaemia. Bilateral occlusion of the external carotid artery plus compression of jugular veins reduced cortical laser-Doppler flow to 11 ± 8% of preischaemic values (P<0.01), flattened the electrocorticogram, and increased mean arterial blood pressure by 17 ± 23% (P<0.01) and intracranial pressure by 161 ± 136% (P<0.01). A rather heterogeneous response was obtained during reperfusion: 14 out of 31 goats showed the ”classical” pattern consisting of hyperaemia followed by delayed hypoperfusion. The remaining goats showed neither hyperaemia (11 goats) nor delayed hypoperfusion (6 goats). The duration of the ischaemic insult did not correlate with the magnitude of hyperaemia or delayed hypoperfusion, but influenced neurodegeneration: while no loss of hippocampal CA1 neurons was observed at 7 days after 5 or 10 min ischaemia, a 68% cell loss was observed in the 20-min ischaemia group. Our goat model has thus proven to be very suitable for the induction of global cerebral ischaemia in a large-animal species without extensive surgery. It allows reproducible reductions of cerebral blood flow, long-term recovery, low mortality rate, and high incidence of neuronal damage. The results reported here support the view that delayed hypoperfusion is not an important determinant of neuronal injury. Received: 23 September 1997 / Received after revision and accepted: 3 December 1997     

Suppression of epileptiform burst discharges in CA3 neurons of rat hippocampal slices by the organic calcium channel blocker,verapamil

Summary We studied the effects of the organic calcium channel blocker, verapamil, on spontaneous and bicuculline-induced epileptiform burst discharges in CA3 pyramidal cells of hippocampal slices. A transient increase of burst discharge rate was observed in most cells within 30 min after the addition of verapamil (100 M) to the perfusing medium. Prolonged verapamil perfusions gradually reduced the rate and duration of burst discharges, then abolished them in all tested slices (over periods of 50–150 min) without blocking synaptic transmission. Responses to intracellular injections of current pulses were also gradually affected by verapamil: Action potential amplitude was decreased, action potential duration increased, frequency adaptation increased, amplitude of the fast hyperpolarization following a single action potential decreased, and amplitude and duration of the slow afterhyperpolarization markedly reduced. The amplitude of calcium spikes elicited in slices perfused with tetrodotoxin-containing medium was not affected by verapamil, but the mean velocity of depolarization near the peak of the calcium spike was decreased. Membrane resting potential and input resistance were not affected by verapamil. These results confirm that verapamil is able to suppress epileptiform activity, but suggest that this effect is rather non-specific, due to inhibition of both postsynaptic sodium and calcium conductances.     

Distinctive morphology of hippocampal CA1 terminations in orbital and medial frontal cortex in macaque monkeys

The fine morphology of hippocampal connections to the orbital and medial frontal cortex (OMFC) was investigated by placing injections of anterograde tracers in the CA1 in two monkeys. The axons terminated mainly in layers 2 and 3, of areas 11, 13, 14c, 25, and 32, and were widely divergent in these layers, traversing 2–4 mm. Boutons were scattered along the main axon, but also occurred as distinctive small, spherical clusters of terminations (“mini-clusters”; diameter <50 μm). Occasional larger terminal arbors were observed in layer 3 and these were often unusually tortuous or convoluted. These features may imply a specialized microcircuitry of hippocampal-OMFC connections, including an origin from a particular subpopulation of CA1 projection neurons.     

Defective neutrophil and lymphocyte function in leucocyte adhesion deficiency.

We report a Chinese girl with the moderate phenotype of leucocyte adhesion deficiency (LAD), presenting with persistent omphalitis and recurrent soft tissue infections. She had subnormal adhesion-dependent neutrophil functions, such as chemotaxis and chemiluminescence response to a particulate stimulant (opsonised zymosan). Despite her adequate humoral response to documented herpes simplex virus type 1, parainfluenza type 2 and adenovirus infection in vivo, there was marked impairment in the generation of plaque-forming cells (PFC) driven by pokeweed mitogen (PWM) in vitro. IgM PFC were less severely affected than IgG and IgA PFC, probably because IgM production is less dependent on T cell help than IgA and IgG production. The patient's B cells and accessory cells had reduced function compared with the control subsets, while helper function of her CD4+ cells was virtually absent in the PWM-driven PFC assay. She also had marked defect in natural killer cell activity. The proliferation of her lymphocytes was normal to several plant lectins, including phytohaemagglutinin, concanavalin A and PWM, but markedly defective to OKT3.     

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

It is widely accepted that the hippocampus plays a major role in learning and memory. The mossy fiber synapse between granule cells in the dentate gyrus and pyramidal neurons in the CA3 region is a key component of the hippocampal trisynaptic circuit. Recent work, partially based on direct presynaptic patch-clamp recordings from hippocampal mossy fiber boutons, sheds light on the mechanisms of synaptic transmission and plasticity at mossy fiber synapses. A high Na⁺ channel density in mossy fiber boutons leads to a large amplitude of the presynaptic action potential. Together with the fast gating of presynaptic Ca²⁺ channels, this generates a large and brief presynaptic Ca²⁺ influx, which can trigger transmitter release with high efficiency and temporal precision. The large number of release sites, the large size of the releasable pool of vesicles, and the huge extent of presynaptic plasticity confer unique strength to this synapse, suggesting a large impact onto the CA3 pyramidal cell network under specific behavioral conditions. The characteristic properties of the hippocampal mossy fiber synapse may be important for pattern separation and information storage in the dentate gyrus-CA3 cell network.     

The dendritic morphology of hippocampal dentate granule cells varies with their position in the granule cell layer: a quantitative Golgi study

Summary The dendritic morphology of Golgistained hippocampal dentate granule cells was evaluated by measuring the amount and location of dendrite, and the number of length of dendritic branches. Granule cells with somata in the superficial third of the granule cell layer had substantially more dendritic material than those with somata in the deep portions of the cell layer; this difference occurred throughout the extent of the molecular layer. Superficial cells also had different dendritic branching patterns and wider dendritic fields than did cells located in the deeper two-thirds of the granule cell layer. These results indicate that the position of neurons within the cell layer should be taken into account when quantifying the dendritic fields of dentate granule cells.     

Age-related changes of astorocytes, oligodendrocytes and microglia in the mouse hippocampal CA1 sector

We investigated the age-related alterations of astorocyte, oligodendrocyte and microglia in the mouse hippocampal CA1 sector under the same conditions using immunohistochemistry. Glial fibrillary acidic protein (GFAP), 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and isolectin B(4) immunoreactivity was measured in 2-, 8-, 18-, 40-42- and 50-59-week-old mice. Total number of GFAP-positive cells was unchanged in the hippocampal CA1 sector up to 40-42 weeks of birth. In 50-59-week-old mice, however, a significant increase in the number of GFAP-positive cells was observed in the hippocampal CA1 sector, exhibiting the morphology of reactive astrocytes. In contrast, the fibers of CNPase immunoreactivity were unchanged in the hippocampal CA1 sector up to 18 weeks of birth. In 40-42- and 50-59-week-old mice, however, a significant decrease in the densities of CNPase-positive fibers was observed in the hippocampal CA1 sector. On the other hand, total number of isolectin B(4)-positive cells was unchanged in the hippocampal CA1 sector up to 40-42 weeks of birth. In 50-59-week-old mice, however, a significant decrease in the number of isolectin B(4)-positive cells was observed in the hippocampal CA1 sector. Our results show that astrocytes proliferate and are activated in the hippocampal CA1 sector with advancing age. Furthermore, the present study demonstrates that the fibers of oligodendrocytes and total number of microglial cells in the hippocampal CA1 sector are decreased during ageing processes. These results suggest that age-related changes of astorocytes, oligodendrocytes and microglia had occurred in the mouse hippocampal CA1 sector.