Granule Cell Nuclei Research Articles

Granule cell proliferation and axon terminal degradation in the dentate gyrus of gerbils (Meriones unguiculatus) during maturation, adulthood and aging.

The objective of the present study was to examine both naturally occurring degrading events in axon terminals of the dentate gyrus and granule cell proliferation in the dentate gyrus of gerbils (Meriones unguiculatus) throughout postnatal life. For that purpose, (1) a selective silver staining technique was applied to analyze neuronal lysosome accumulation (LA), indicating synaptic degradation during development. LA was quantified by counting silver grains in the inner third and outer two thirds of the molecular layer, granular layer, subgranular layer and the hilus of the dentate gyrus. (2) Proliferation of granule cells was identified by in-vivo labeling with 5-bromo-2'-desoxyuridine (BrdU). BrdU-labeled granule cell nuclei were identified in consecutive horizontal slices along the mid-septotemporal axis of the hippocampus and light-microscopically quantified 4h after the BrdU-labeling. It was found (1) that in young animals LA significantly increased within all layers and reached adult levels after about 3 months. During subsequent development LA kept on this level throughout aging with highest values within the inner molecular layer. (2) There was a highly significant temporal gradient in granule cell proliferation with numbers of BrdU-labeled cells exponentially declining during juvenile life. Nevertheless, granule cell proliferation occurred throughout adult life and aging. The present results are discussed (1) with concepts of ongoing neuroplasticity and remodeling of neuronal networks in the developing and adult brain, and (2) with regard to pharmacologically induced neuromorphogenesis.

Ultrastructural localization of activated NF-kappaB in granule cells of the rat fascia dentata.

The distribution of activated NF-kappaB (p65) was studied in granule cells of the rat fascia dentata using confocal laser scanning microscopy and preembedding immunogold electron microscopy. Activated NF-kappaB, detected with a monoclonal antibody specific for the nuclear localization signal-epitope, was found in proximal dendrites, somata, and nuclei but not in axon terminals of granule cells. Within the nuclei of granule cells, clusters of NF-kappaB immunoreactivity were detected. These data are in line with the proposed function of NF-kappaB as a retrograde signal transducer which transports information from synaptic sites to the nucleus to initiate gene expression.

Adult treatment with methamphetamine transiently decreases dentate granule cell proliferation in the gerbil hippocampus.

The objective of the present study was to examine whether acute treatment with the recreational drug methamphetamine influences adult granule cell proliferation in the dentate gyrus of the hippocampus. For that purpose, at the age of postnatal day 90 adult male gerbils (Meriones unguiculatus) received a single dose of either methamphetamine (25 mg/kg; i.p.) or saline. Proliferation of granule cells was identified by in-vivo labeling with 5-bromo-2'-desoxyuridine (BrdU) which was applied either simultaneously with methamphetamine or 36 h after administration of the drug. BrdU-labeled granule cell nuclei were identified in consecutive horizontal slices along the mid-septotemporal axis of the hippocampus and light-microscopically quantified 7 days after the BrdU-labeling. It was found that in both saline- and methamphetamine-treated animals there was a highly significant spatial septotemporal gradient in granule cell proliferation with numbers of BrdU-labeled cells gradually declining from the septal towards the temporal pole. The acute treatment with methamphetamine suppressed granule cell proliferation by about 28% and the septotemporal gradient of mitotic activity became significantly attenuated. It was further found that 36 h after the drug challenge granule cell proliferation rates had been restored almost to the control values along the whole septotemporal axis of the hippocampus. The present results are discussed with regard to (1) pharmacological regulation of neurogenesis in the hippocampus and (2) probable clues they may provide for both understanding the biological correlates of psychotic disorders and evolution of future concepts in neuropharmacological intervention.

Age and Organ Dependent Spontaneous Generation of Nuclear 8-Hydroxydeoxyguanosine in Male Fischer 344 Rats

8-Hydroxydeoxyguanosine (8-OHdG) is a major oxidative DNA adduct playing roles in senescence, carcinogenesis and various disease processes. High-performance liquid chromatography with an electrochemical detection (HPLC-ECD) method has been widely used to assess organ levels of 8-OHdG, and a recently introduced immunohistochemical approach has made it possible to clarify intra-organ localization. In the present study, these methods were employed to reveal age-dependent changes in nuclear 8-OHdG within various tissues of male Fischer 344 rats between 18 fetal days and 104 weeks of age. 8-OHdG was detected in the nuclei of cerebellar small granule and small cortical cells, cerebral nerve cells, and choroid plexus epithelia of the brain and ependymal cells of the spinal cord; parenchymal cells in the anterior lobe of the pituitary and adrenal glands (mainly cortex); bronchial epithelium of the lung; intra-hepatic bile duct, pancreatic duct, glandular gastric and intestinal epithelial cells; renal tubular epithelial cells (mainly medulla); and spermatogonia and spermatocytes of the testis and seminal vesicle epithelia. The nuclear 8-OHdG levels were high (more than two lesions per 106 deoxyguanosines) from 7 days to 104 weeks of age in the brain, 3 to 6 weeks in the adrenal gland, 6 to 104 weeks in the lung, and 3 to 52 weeks in the testis. In the other organs, the nuclear 8-OHdG levels remained low throughout. These findings provide a basis for research dealing with oxidative stress by indicating organ-specific and age- but not aging-dependent changes in the localization of spontaneously generated nuclear 8-OHdG in intact rats. The immunohistochemical approach has advantages for assessing variation of 8-OHdG formation at the cellular level not accessible to the HPLC-ECD method.

Quantitative age-changes in endoplasmic reticulum and nucleus of cerebellar granule cells ☆

A stereological study was performed on cerebellar granule cells from rats 2 to 24 months of age (eight different ages, five animals per age group) to quantify age-related alterations in the rough endoplasmic reticulum (RER). The mean surface density and the mean total surface area of the nucleus, as well as the mean absolute volume of euchromatin per cell, were also estimated to examine whether or not these had quantitative relationships with the RER. The mean surface density and the mean total surface area of RER per cell changed significantly, attaining maximum values at 24 months of 1733 μm 2/1000 μm 3 (0.06) and 64 μm 2 (0.03), respectively, (coefficients of variation in parentheses). The corresponding values at 2 months were 706 μm 2/1000 μm 3 (0.20) and 26 μm 2 (0.24). The mean absolute volume of the euchromatin changed significantly, with a minimum value of 57 μm 3 (0.05) occurring at 21 months. We postulate that the increase in RER may be part of a mechanism that compensates for an age-related decrease in euchromatin. An increase in the RER network may improve intracellular transport of proteins, production of which is apparently diminished with aging. The increase may also compensate for the reported decrease in calcium buffer capacity of smooth endoplasmic reticulum.

A single neonatal dose of methamphetamine suppresses dentate granule cell proliferation in adult gerbils which is restored to control values by acute doses of haloperidol

A single non-invasive dose of methamphetamine (50 mg/kg; i.p.) was administered to neonatal male gerbils (Meriones unguiculatus) aged 14 days. The first objective of the present study was to examine whether this early drug challenge, which has been shown to induce suppressive postnatal maturation of prefrontal dopamine (DA) innervation (Dawirs et al., 1994), interferes with adult granule cell proliferation in the dentate gyrus. Proliferation of granule cells was identified by in-vivo labeling with 5-bromo-2'-desoxyuridine (BrdU). BrdU-labeled granule cell nuclei were identified in consecutive horizontal sections along the mid-septotemporal axis of the hippocampus and light-microscopically quantified 7 days after BrdU-labeling. It was found that a single neonatal dose of methamphetamine was a stimulus strong enough to significantly attenuate adult granule cell proliferation. This effect was clearly lateralized with significant suppression of mitotic activity becoming apparent solely in the left dentate gyrus (-34%). The second objective of the present study was to examine whether acute doses of haloperidol, which have been found to stimulate granule cell proliferation in healthy adult animals (Dawirs et al., 1988), might restore mitotic activity to control values. For that purpose, at the age of postnatal day 90 adult animals which had been challenged with methamphetamine as juveniles received 4 doses of haloperidol (5 mg/kg; i.p.). Proliferation of granule cells was identified by BrdU-labeling. It was found that this neuroleptic treatment acutely restored granule cell proliferation rates to control values. The present results are discussed with regard to (1) factors, regulating mitotic activity in the hippocampus and (2) probable clues they may provide for understanding the neurobiological basis of psychotic behavior.

Adult treatment with haloperidol increases dentate granule cell proliferation in the gerbil hippocampus.

Male gerbils were bred and reared grouped under enriched semi-natural environmental conditions. The objective of the present study was to examine the influence of an acute treatment with the neuroleptic haloperidol on adult granule cell neurogenesis in the hippocampus. For that purpose, at the age of postnatal day 90 adult animals received 4 challenges of either haloperidol (5 mg/kg, i.p.) or saline. Proliferation of granule cells was identified by in-vivo labeling with 5-bromo-2'-desoxyuridine (BrdU) which was applied 1 hour after the final dose of haloperidol. BrdU-labeled granule cell nuclei were identified in consecutive horizontal slices along the mid-septotemporal axis of the hippocampus and light-microscopically quantified 7 days after the BrdU-labeling. It was found that in both saline- and haloperidol-treated animals there was a highly significant spatial septotemporal gradient in granular cell proliferation with numbers of BrdU-labeled cells gradually declining from the septal towards the temporal pole. The acute treatment with haloperidol stimulated granule cell proliferation by about 75% and the septotemporal gradient of mitotic activity became significantly enhanced. The present results are discussed with regard to known factors regulating cell proliferation in the hippocampus and other cell systems.

Granule cell apoptosis and protein expression in hippocampal dentate gyrus after forebrain ischemia in the rat

We investigated the relationship between apoptosis and selective protein expression in brain from rats subjected to 8 ( n=10) or 12 min ( n=10) of forebrain ischemia and 48 h of reperfusion, and control sham operated ( n=2) and normal ( n=2). Coronal sections were processed for double staining with DNA fragmentation detection and immunohistochemical staining. In five of ten 8-min ischemic and three of ten 12-min ischemic animals, nearly all dead granule cells within the dentate gyrus exhibited apoptotic morphology. In the remaining animals, no granule cell death was evident. In the pyramidal regions (CA1/2), nearly all dead cells were necrotic with only scattered apoptotic cells present. The immunoreactive expression of wt-p53, p53-response proteins (WAF1, Bax and Gadd45), and a cell cycle protein (cyclin D) were detected and preferentially localized to nuclei of apoptotic granule cells, and were weakly expressed in nuclei of necrotic pyramidal CA1/2 cells. Thus, 48 h after 8 or 12 min of forebrain ischemia in the rat, most pyramidal cells and dentate granule cells undergo distinct cell death pathways of necrosis or apoptosis, respectively. In addition, the selective expression of proteins associated with DNA damage and cell cycle in apoptotic dentate granule cells suggests a role for these proteins in the induction of apoptosis.

TheIn VivoTime Course for Elimination of Adrenalectomy-Induced Apoptotic Profiles from the Granule Cell Layer of the Rat Hippocampus

Although apoptotic cellular degeneration has been reported to be extremely rapid with the use of in vitro models, the time needed to clear apoptotic neurons in the in vivo brain is unknown. In this study we used a simple morphological approach to solve this problem. Four days after adrenalectomy (ADX), all of the operated rats morphologically displayed hippocampal granule cell apoptosis that was prevented completely by corticosterone replacement immediately after ADX. Therefore, we intravenously injected the rats with corticosterone 4 d after ADX and subsequently maintained them on corticosterone replacement in saline drinking water. This corticosterone replacement could protect healthy granule cells promptly and continuously against hormone-deficient apoptosis, because the normal glucocorticoid receptor immunoreactivity within the granule cell nuclei, which disappeared after ADX, was identified 1 hr after corticosterone replacement was started, and this effect persisted for several days. However, this corticosterone treatment could not prevent the irreversible apoptosis of the already degenerated granule cells at various stages of the same progressive apoptotic process. Then we successively traced the disappearance of apoptotic granule cells throughout the hippocampus at different time points by Nissl and silver staining. Given that the apoptotic cells at the earliest stage of the degenerating process when the ADX rats received corticosterone injection were the last to disappear, the period from corticosterone injection until the disappearance of the last degenerating debris of apoptotic cells was taken to represent the time course for elimination of apoptotic neurons in vivo. We discovered that the elimination of apoptotic granule cells took 72 hr.

A Stereological Study on the Nuclear Volume of Cerebellar Granule Cells in Aging Rats

A morphometric study on age changes of rat cerebellar cortex ( Crus I and Crus II) was carried out. The nuclear volume of the granule cells was estimated by means of two unbiased stereological methods: the nucleator, which enabled the estimation of the number-weighted mean volume (V̄ N), and the point-sampled intercepts method, allowing the determination of the volume-weighted mean volume (V̄ V). These parameters enabled the estimation of the coefficient of variation of nuclear volume in the number-weighted distribution [CV(V N)]. All parameters were determined in eight age groups (2, 6, 9, 12, 15, 18, 21, and 24 months—five animals per age) and the mean values of each age group were compared using one-way ANOVA with post hoc comparisons, and regression analysis. It was demonstrated for the first time, using unbiased techniques, that the nucleus of granule cells of the cerebellar cortex showed a significant decrease in its mean volumes (V̄ V) with age, especially from 21 months onwards. Although CV(V N) was not correlated with age, it was also demonstrated that these cells bear a considerable nuclear size pleomorphy that was maintained throughout the age spectrum.

Apoptotic cell death in the cerebellum of mutant weaver and lurcher mice

Apoptosis in the central nervous system of mutant weaver (wv) and lurcher (Ic) mice was studied using in situ DNA end-labeling. The number of apoptotic cells in the external granule cell layer of weaver (wv/+) mice at postnatal day 9 was increased six- to eight-fold compared to (+/+) littermates. Purkinje cells and Bergmann glia cells were not affected. No labeled cells were found in the substantia nigra. In lurcher (lc/+) mice, labeled nuclei of large cells were found in the Purkinje cell layer, suggesting that Purkinje cells of mutant lurcher mice undergo apoptosis. Apoptotic granule cell nuclei were found in the internal granule cell layer. In contrast to weaver (wv/+) mice, the number of apoptotic cells in the external granule cell layer was not increased. Apoptosis appears to be the common pathway of cell death in the degenerative processes induced by the weaver and the lurcher gene, respectively. These mutant mice offer the opportunity to study the mechanisms that underlie inappropriate apoptotic cell death in vivo.

Fos protein immunoreactivity in the developing olfactory bulbs of normal and naris-occluded rats

Immediate early genes such as c- fos may be a route through which extracellular events affect genomic expression. Expression of immediate early genes is important in the transcriptional regulation necessary for the normal development of the nervous system. Developmental patterns of Fos protein (the product of c- fos immediate early gene expression) were studied in the main olfactory bulb of the rat using immunocytochemistry. Embryonic Day 21 (E21, the last prenatal day), as well as Postnatal Day 0 (P0), P1, P5, P10, P15, P20 and P30 subjects were examined. Although staining was absent in the E21 bulb, there was a rapid onset of Fos synthesis within hours after birth. Distribution of Fos-immunoreactive (Fos-ir) nuclei corresponded to the sequence of bulb maturation: numerous mitral/tufted and granule cells were labeled on P0, followed by the appearance of Fos-ir in the nuclei of periglomerular cells and an increase in the number of stained granule cells with development. Surgical closure of an external naris on P1 resulted in a 70% reduction in the number of Fos-ir granule cell nuclei as early as 2 h after the manipulation. During the next 30 days, levels of Fos staining further diminished in experimental bulbs when compared to their contralateral controls. Nevertheless, electrical stimulation of the contralateral bulb in P20 pups resulted in a robust increase of Fos labeling in most main and accessory olfactory bulb mitral cells and in many granule and periglomerular neurons, suggesting that the experimental bulbs remain competent to express Fos protein.

Increase of c-fos and ras oncoproteins in the denervated neuropil of the rat dentate gyrus

When the entorhinal cortical input to the rat dentate gyrus is destroyed, the process of sprouting and synaptogenesis begins within the denervated dendritic laminae. The present study used immuno-histochemical methods to determine whether there was an increase in the oncoproteins c-fos and ras within the denervated neuropil of the dentate gyrus during this period of terminal growth and synapse formation. Animals were prepared for immunolabeling one, three, six and 30 days after unilateral lesion of the entorhinal cortex. Rats were perfused with paraformaldehyde fixative and brain sections were incubated with antibodies to either c-fos or ras oncoprotein. Qualitative light microscopic analysis showed a marked increase in both c-fos and ras proteins over the denervated zone at three days postlesion when compared to both the intact contralateral control and the naive control. At one- and six-day postlesion intervals there was also an increase in labeling over the denervated neuropil with each oncoprotein; however, the intensity of label was reduced relative to that of the three-day time interval. No increase in labeling over the denervated zone was visible for either antibody at 30 days postlesion. The high level of both c-fos and ras labeling in the denervated molecular layer was confirmed with Western blot analysis of dissected molecular layers from lesioned and contralateral control hippocampi. Controls for antibody and method specificity showed that the labeling was specific for c-fos and ras proteins. The high level of c-fos labeling over the denervated molecular layer was uniform, with scattered punctate sites of reaction product interspersed in the neuropil. Glial cell bodies in the neuropil contained the highest levels of c-fos oncoprotein. The granule cell nuclei showed an apparent reduction in the level of c-fos labeling at one, three and six days postlesion when compared with the nuclear staining of naive control cases. At 30 days postlesion, high levels of labeling over the denervated zone were not visible and c-fos localization had returned to the typical predominant nuclear sites seen in controls. Ras oncoprotein localization was diffuse in the cell processes of the molecular layer, with intermittent glial labeling within the denervated zone. No cell nuclei labeling was observed with antibodies to ras protein. These results show that both c-fos and ras oncoproteins are increased within the denervated neuropil of the dentate gyrus during sprouting and synapse formation. Our study suggests that neuropil alterations in gene expression through c-fos, and membrane signal transduction by ras may be part of the cellular mechanisms invoked during lesion-induced synaptogenesis.

The expression of the immediate-early genes c-fos, egr-1 and c-jun in the accessory olfactory bulb during the formation of an olfactory memory in mice

Female mice form a memory for the pheromones of the male with which they mate. It has been proposed that the site of the synaptic changes underlying this memory is the accessory olfactory bulb, at the first level of the accessory olfactory system. In this study we have examined the expression of the immediate-early genes c-fos, c-jun and egr-1 in the mitral and granule cells of the accessory olfactory bulb immediately after mating, during the period of memory formation. Transient increases were seen in the number of granule cell nuclei expressing c-fos and the number of granule and mitral cell nuclei expressing egr-1, during the period of memory formation. No changes were observed in the expression of c-jun during this period. The increase in the number of cells expressing c-fos and egr-1 required the association of mating and pheromonal exposure, conditions also required for memory formation. Large increases in the number of mitral and granule cell nuclei expressing c-fos and egr-1 were also observed following the infusion of the drug bicuculline into the accessory olfactory bulb in the absence of mating. This procedure has previously been shown to result in the formation of a nonspecific memory for male pheromones. These results associate the expression of c-fos and egr-1 in the accessory olfactory bulb with the conditions required for the formation of an olfactory memory for male pheromones.

Long-term expression of the c-fos protein during the in vitro differentiation of cerebellar granule cells induced by potassium or NMDA

Levels of the c-fos protein were assayed in mouse cerebellar granule cell during their in vitro development under different culture conditions. When grown in media favoring both their survival and differentiation, i.e. in the presence of 30 mM K + or 12.5 mM K + plus 100 μM N- methyl- d-aspartate (NMDA), the c-fos protein becomes detectable in the nucleus of granule cells on and after 6 days and persists to high levels until the culture begins to decline. The protein c-fos appears therefore after the critical period described for the survival effect of K + depolarization or NMDA receptor stimulation which corresponds to days 2–5 after plating. The c-fos protein remains however scarcely detectable or undetectable throughout the life-span of cells cultured under conditions providing poor survival and differentiation, i.e. in the presence of low K + (5 or 12.5 mM) alone or when the effect of NMDA is blocked by the NMDA receptor antagonist MK-801. Interestingly, in cortical and striatal neurons, the survival and differentiation of which being not affected by depolarizing media, no c-fos protein is detected whatever the culture conditions tested at least during the first 18 days in vitro. This suggests that long-term expression of the c-fos gene might be related to some aspect of the late in vitro differentiation process of cerebellar granule cells.

Immunofluorescence localization of thyroid hormone receptor protein beta 1 and variant alpha 2 in selected tissues: cerebellar Purkinje cells as a model for beta 1 receptor-mediated developmental effects of thyroid hormone in brain.

Rat c-erbA beta 1 mRNA rises in cerebrum during the first 10 days of life, coincident with an increase in tissue triiodothyronine (T3) levels and T3-dependent brain development. These data suggest that the beta 1 receptor may mediate the T3 effect. However, in cerebellum c-erbA beta 1 mRNA levels were very low. Since cerebellar development, including dendritic arborization of Purkinje cells, is a T3-sensitive process, we assessed the levels of the beta 1 receptor protein in cerebellum during development. Antisera to unique peptide regions of beta 1 were raised. Their specificity was demonstrated by specific immunoprecipitation of the in vitro translated product, 85% immunoprecipitation of the T3 binding activity in hepatic nuclear extracts, and Western blot analysis of tissue extracts. Immunohistochemical studies using anti-beta 1 antiserum stained liver nuclei but not testis nuclei, which contain no T3 binding activity or beta 1 mRNA. In cerebellar Purkinje cells, an immunofluorescent signal, localized to the nucleus and more intense than that seen in the liver, was observed. A positive but weaker signal was also present in the granule cells. Thus, we may infer that the cerebellum contains significant concentrations of beta 1 receptor protein despite the low beta 1 mRNA content. Both the intensity of staining in Purkinje cell nuclei and immunoprecipitable beta 1 receptor binding capacity rose in the neonatal period. Antiserum to the non-T3 binding alpha 2 variant protein was also prepared and a distinctive pattern of fluorescence was observed. Strong fluorescence was seen in the nuclei of granule cells, but none was seen in Purkinje cells. The alpha 2 fluorescence in testis was high, consistent with the high levels of alpha 2 mRNA in this tissue. The fluorescent signal appeared to originate primarily in dividing spermatogonia. Our findings support the concept that the beta 1 receptor plays a central role in T3-induced brain development and strongly suggest that the Purkinje cell is a direct target for T3.

Nuclear and axonal localization of Ca2+/calmodulin-dependent protein kinase type Gr in rat cerebellar cortex.

The granule cell-enriched Ca2+/calmodulin-dependent protein kinase (CaM kinase-Gr) is a recently discovered neuron-specific enzyme. The kinase avidly phosphorylates synapsin I and contains a polyglutamate sequence, which suggests an association with chromatin as well. A possible role in synapsin I phosphorylation and in nuclear Ca2+ signaling was supported by immunochemical and ultrastructural examination of CaM kinase-Gr distribution. CaM kinase-Gr immunoreactivity was present in the molecular and granule cell layers of the rat cerebellum. This pattern corresponded to the occurrence of the enzyme in the granule cell axons and nuclei, respectively. Immunoblots confirmed these findings. Thus, CaM kinase-Gr may mediate and coordinate Ca2(+)-signaling within different subcellular compartments.

Expression and quantitative changes of carbonic anhydrase in developing neurones of rat central nervous system

Postnatal changes in carbonic anhydrase activity were investigated in the islands of Calleja, which have been previously reported to contain the enzyme. Results obtained with a new modified method of Hansson provided further evidence for the distinction between the medial and lateral islands of Calleja. The enzyme was localized mainly in the nucleus and cytoplasm of granule cells without showing binding to any cytoplasmic organelle. No large neurons of the islands displayed carbonic anhydrase reactivity. The time course and rate of increase of carbonic anhydrase expression were different in the giant island of Calleja and lateral islands and this finding may strengthen the hypothesis regarding the medio-lateral diversity of Calleja's islands. On the other hand, at the end of the maturation process the granule cell complexes showed no significant difference in the proportion of carbonic anhydrase positive neurones. The almost equal rate of appearance of carbonic anhydrase reactive granule cells raises the possibility of a basic common role of both medial and lateral islets.

New strains of seizure-prone mice

The origins of two new strains of seizure-prone mice are provided, and some of their behavioral characteristics are described. Comparison of the hippocampal granule cell layer of one of the new strains with the two inbred strains from which it was derived revealed strain differences in the diameter of granule cell nuclei and in the number of granule cells in the suprapyramidal blade. Basket cell counts did not differ between the strains, but both basket cell and granule cell number were consistently higher for the suprapyramidal blade than for the infrapyramidal blade. The existence of these and other blade differences suggests that the two blades will prove to be functionally distinctive neuronal systems.

A Morphometric Ultrastmctural Study of the Nucleus of Cerebellar Granule Cells

A quantitative approach to the nuclear ultrastructure of cerebellar granule cells is described here. The study was made using conventional electron microscopy from cerebellar cortices of adult rats by means of a semiautomatic image analyzer. The basic observation is that the nuclei of mature granule cells constitute a homogeneous population in terms of morphometric and stereologic data; in fact, the volume density of condensed chromatin within the nuclei remains practically constant in all nuclear sections. These results seem to indicate the existence of a cell-specific nuclear morphometric phenotype which might be considered as an effective criterion for the typification of this cellular lineage.