Cerebellar Layer Research Articles

Aging-associated modulation in the expression of Pax6 in mouse brain.

Symptoms like mental retardation, depression, and anxiety have been observed during aging. Almost similar phenotypes have been evident in patients having haploinsufficiency or mutations in Pax6, a transcriptional regulator. Since Pax6 regulates axon guidance, differentiation of neurons from glia, and neuronal migration, it has been considered as a marker of newly generated neurons. The immunohistochemical analysis of Pax6 positive cells and expression pattern of Pax6 in olfactory lobe, hippocampus, and cerebellum of aging mouse brain have been investigated. The number of Pax6 positive cells and level of Pax6 were reduced progressively in olfactory lobe, cerebellum, and hippocampus from postnatal day-zero (P0) to old age mice. Pax6 positive cells were significantly lower in dentate gyrus, CA1, CA2, and CA3 regions of hippocampus, in mitral cell (MiCe), and internal plexiform (InPl) layers of olfactory lobe, and in granular cell (GrLa), and Purkinje's cell (PuCe) layers of cerebellum from P0 to old age. Thus, modulation in the expression of Pax6 and reduction in Pax6 positive cells show direct association of Pax6 with aging-related neuronal dystrophy.

Hereditary Cerebellar Degenerative Disease (Cerebellar Cortical Abiotrophy) in Rabbits

A pair of rabbits gave birth to a set of littermates (F1) with symptoms of early-onset ataxia. Microscopic examination revealed cerebellar degenerative disease in 5 of 6 littermates. Light microscopy was used to compare the thickness of each cerebellar layer in affected animals in contrast to a normal control. Affected animals showed narrowing of the molecular layer of the vermis, reduced density of Purkinje cell dendrites and irregular thickness in their branchlets, and reduced density of granular cells and scattered pyknotic cells in the granular layer. Pyknotic cells were apoptotic granular cells, confirmed by positive staining using the TUNEL method. Electron microscopy confirmed the thinning of the molecular layer seen by light microscopy and also showed a reduced number of parallel fibers, which indicate granular cells axons, and a reduced number of synaptic junctions between Purkinje and granular cells. Purkinje cells had electron-dense, irregularly shaped cytoplasm with irregularly shaped nuclei, and some of these cells had a central chromatolysis-like region. These findings support a diagnosis of cerebellar cortical abiotrophy, a hereditary condition that causes nerve function impairment leading to early-onset progressive degeneration of the cerebellar cortex.

Encephalitis and Neuronal Necrosis in a 3-Month-Old Suckled Beef Calf

A 3-month-old suckled beef calf from the west coast of Scotland showed neurologic clinical signs for 1 week and was euthanized after failing to respond to treatment. Blood and tissue samples, including the brain, were submitted for diagnosis. Histologic examination of the brain showed neuronal chromatolysis and necrosis in the hind brain and loss of Purkinje cells in the cerebellum, accompanied by mild nonsuppurative encephalitis in the hind brain with a striking lack of inflammation in the cerebellar layers. Other microscopic lesions present were mild nonsuppurative meningitis with perivascular cuffs, diffuse hypergliosis, and occasional foci of neuronophagia. Polymerase chain reaction amplification of viral nucleic acids and specific immunohistochemical labeling allowed the identification of louping ill virus, and serology showed high titers of immunoglobulin M, indicating a recent infection.

Signals and circuits in the Purkinje neuron

Purkinje neurons (PN) in the cerebellum have over 100,000 inputs organized in an orthogonal geometry, and a single output channel. As the sole output of the cerebellar cortex layer, their complex firing pattern has been associated with motor control and learning. As such they have been extensively modeled and measured using tools ranging from electrophysiology and neuroanatomy, to dynamic systems and artificial intelligence methods. However, there is an alternative approach to analyze and describe the neuronal output of these cells using concepts from electrical engineering, particularly signal processing and digital/analog circuits. By viewing the PN as an unknown circuit to be reverse-engineered, we can use the tools that provide the foundations of today’s integrated circuits and communication systems to analyze the Purkinje system at the circuit level. We use Fourier transforms to analyze and isolate the inherent frequency modes in the PN and define three unique frequency ranges associated with the cells’ output. Comparing the PN to a signal generator that can be externally modulated adds an entire level of complexity to the functional role of these neurons both in terms of data analysis and information processing, relying on Fourier analysis methods in place of statistical ones. We also re-describe some of the recent literature in the field, using the nomenclature of signal processing. Furthermore, by comparing the experimental data of the past decade with basic electronic circuitry, we can resolve the outstanding controversy in the field, by recognizing that the PN can act as a multivibrator circuit.

Antineuronal Antibodies in Migraine Patients With White Matter Lesions

ABSTRACTMagnetic resonance imaging (MRI) studies occasionally display focal hyperintense lesions within the white matter of migraine patients. No immunological factors associated with these lesions have been defined so far. To investigate the relationship between MRI lesions and antineuronal antibody response, 17 migraine patients with white matter lesions (WML), 19 migraine patients without WML, 20 multiple sclerosis patients with WML and with no headache history, and 20 healthy individuals were enrolled, and their sera were examined by indirect immunohistochemistry for the presence of immunoglobulin G (IgG) reacting with the rat brain tissue. Migraine patients with and without WML essentially showed identical demographic and clinical features and frequencies of systemic autoantibodies. However, migraine patients with WML displayed a significantly higher frequency of antineuronal antibodies than those without WML (12/17 vs. 2/19, p = .0004). Serum IgG of migraine patients predominantly reacted with the cytoplasm of neurons and the molecular layer of cerebellum. None of the multiple sclerosis patients and healthy controls displayed antineuronal antibodies. Our results imply the involvement of inflammation in migraine pathogenesis.

Widespread Proliferation Impairment and Hypocellularity in the Cerebellum of Fetuses with Down Syndrome

Evidence in mouse models for Down syndrome (DS) and human fetuses with DS clearly shows severe neurogenesis impairment in various telencephalic regions, suggesting that this defect may underlie the cognitive abnormalities of DS. As cerebellar hypotrophy and motor disturbances are part of the clinical features of DS, the goal of our study was to establish whether these defects may be related to neurogenesis impairment during cerebellar development. We found that in fetuses with DS (17-21 weeks of gestation) the cerebellum had an immature pattern, a reduced volume and notably fewer cells (-25%/-50%) in all cerebellar layers. Immunohistochemistry for Ki-67, a marker of cycling cells, showed impaired proliferation (-17%/-50%) of precursors from both cerebellar neurogenic regions (external granular layer and ventricular zone). No differences in apoptotic cell death were found in DS vs. control fetuses. The current study provides novel evidence that in the cerebellum of DS fetuses there is a generalized hypocellularity and that this defect is due to proliferation impairment, rather than to an increased cell death. The reduced proliferation potency found in the DS fetal cerebellum, in conjunction with previous evidence, strengthens the idea that the trisomic brain is characterized by widespread neurogenesis disruption.

Ionic Matrix for Enhanced MALDI Imaging Mass Spectrometry for Identification of Phospholipids in Mouse Liver and Cerebellum Tissue Sections

The ionic matrix (IM) is considered to be versatile for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for the identification of a wide range of biomolecules due to its good solubility for a variety of analytes, formation of homogeneous crystals with analytes, and high vacuum stability. When these advantages are exploited, the performance of IM of α-cyano-4-hydroxycinnamic acid butylamine (CHCAB) and 2,5-dihydroxybenzoic acid butylamine (DHBB) was compared with other matrixes for the identification of phospholipids in standard mixtures and mouse liver tissue sections. The results showed that the IM of CHCAB caused higher signal intensity and allowed the detection of a number phospholipids such as phosphatidylethanolamine (PE) and phosphatidylserine (PS) in addition to detection of phosphatidylcholine (PC) on the surface of the liver tissue sample. The IM of CHCAB was also used to identify the species of lipids present in different layers of cerebellum where the greater numbers of biomolecules were detected as compared to DHB matrix. Further, the feasibility of the proposed method was extended for the analysis of tryptic digested cytochrome c for increased signal intensity and number of peptide sequences in MALDI-MS. Thus, the application of IM to MALDI-MS could be a promising tool for imaging biomolecules in tissue sections in high throughput analyses with high sensitivity.

Origin and timing of voltage-sensitive dye signals within layers of the turtle cerebellar cortex

Optical recording techniques were applied to the turtle cerebellum to localize synchronous responses to microstimulation of its cortical layers and reveal the cerebellum's three-dimensional processing. The in vitro yet intact cerebellum was first immersed in voltage-sensitive dye and its responses while intact were compared to those measured in thick cerebellar slices. Each slice is stained throughout its depth, even though the pial half appeared darker during epi-illumination and lighter during trans-illumination. Optical responses were shown to be mediated by the voltage-sensitive dye because the evoked signals had opposite polarity for 540- and 710-nm light, but no response to 850-nm light. Molecular layer stimulation of the intact cerebellum evoked slow transverse beams. Similar beams were observed in the molecular layer of thick transverse slices but not sagittal slices. With low currents, beams in transverse slices were restricted to sublayers within the molecular layer, conducting slowly away from the stimulus site. These excitatory beams were observed nearly all the way across the turtle cerebellum, distances of 4–6 mm. Microstimulation of the granule cell layer of both transverse or sagittal slices evoked a local membrane depolarization restricted to a radial wedge, but these radial responses did not activate measurable molecular layer beams in transverse slices. White matter microstimulation in sagittal slices (near the ventricular surface of the turtle cerebellum) activated the granule cell and Purkinje cell layers, but not the molecular layer. These responses were nearly synchronous, were primarily caudal to the stimulation, and were blocked by cobalt ions. Therefore, synaptic responses in all cerebellar layers contribute to optical signals recorded in intact cerebellum in vitro ( Brown and Ariel, 2009). Rapid radial signaling connects a sagittally-oriented, fast-conduction system of the deep layers with the transverse-oriented, slow-conducting molecular layer, thereby permitting complex temporal processing between two tangential but orthogonal paths in the cerebellar cortex.

In vivo Structural Imaging of the Cerebellum, the Contribution of Ultra-High Fields

This review covers some of the contributions to date from cerebellar imaging studies performed at ultra-high magnetic fields. A short overview of the general advantages and drawbacks of the use of such high field systems for imaging is given. One of the biggest advantages of imaging at high magnetic fields is the improved spatial resolution, achievable thanks to the increased available signal-to-noise ratio. This high spatial resolution better matches the dimensions of the cerebellar substructures, allowing a better definition of such structures in the images. The implications of the use of high field systems is discussed for several imaging sequences and image contrast mechanisms. This review covers studies which were performed in vivo in both rodents and humans, with a special focus on studies that were directed towards the observation of the different cerebellar layers.

Differential changes in cerebellar transmitter content and expression of calcium binding proteins and transcription factors in mouse administered with amphetamine

Cerebellar mechanisms were explored underlying the effects of amphetamine (Amph) on the brain, by monitoring primarily the neurochemistry of the cerebellum. Adult mice received repeated intermittent injections of d-Amph, 5 mg/kg or saline, twice daily for three days and once on day 4. As revealed by the biochemical analysis, the levels of GABA content were increased by 68–93% in the cerebellar vermis and hemisphere of mice at 4 h after the first (acute) or the last (repeated) Amph injections, though the glutamate content was unaltered, compared to the respective saline-treated controls. By contrast, at 4 h post-repeated Amph, in the vermis, the level of norepinephrine was approximate 38% lower than the corresponding control and 5-hydroxytryptamine (5-HT) resembled the control, whereas in the hemisphere, the norepinephrine content was similar to control and 5-HT 66% higher, implying cerebellar lobe-dependent changes. However, in both lobes, at 4 h after the acute and repeated Amph exposures, changes of the transmitter content were correlated with reductions of 50–64% in the levels of the phosphorylated (p) MAP kinase (K) expression and 39–55% in the calbindin-D28k (CB) of the Purkinje cell somata, and increases of 289–556% in pCREB, 373–594% c-FOS, and 51–76% calretinin of the granular layer, as shown by immunohistochemical analysis. The up-regulated GABA content in the vermis and hemisphere may be associated with the decreased expression of Purkinje somatal CB and pMAPK, implicating a relation between the Ca 2+ of Purkinje cells and the level of GABA. Furthermore, the prominent increases of the granular layer pCREB, c-FOS and calretinin may influence the activity of Purkinje cells, which are known to be modulated by the granule cells. The data indicate that the Amph exposure selectively alters specific transmitters in the cerebellar lobes and modifies the cellular expression of distinct signaling proteins in the cerebellar layers.

Regional distribution and cellular localization of β2‐adrenoceptors in the adult zebrafish brain (Danio rerio)

The beta(2)-adrenergic receptors (ARs) are G-protein-coupled receptors that mediate the physiological responses to adrenaline and noradrenaline. The present study aimed to determine the regional distribution of beta(2)-ARs in the adult zebrafish (Danio rerio) brain by means of in vitro autoradiographic and immunohistochemical methods. The immunohistochemical localization of beta(2)-ARs, in agreement with the quantitative beta-adrenoceptor autoradiography, showed a wide distribution of beta(2)-ARs in the adult zebrafish brain. The cerebellum and the dorsal zone of periventricular hypothalamus exhibited the highest density of [(3)H]CGP-12177 binding sites and beta(2)-AR immunoreactivity. Neuronal cells strongly stained for beta(2)-ARs were found in the periventricular ventral telencephalic area, magnocellular and parvocellular superficial pretectal nuclei (PSm, PSp), occulomotor nucleus (NIII), locus coeruleus (LC), medial octavolateral nucleus (MON), magnocellular octaval nucleus (MaON) reticular formation (SRF, IMRF, IRF), and ganglionic cell layer of cerebellum. Interestingly, in most cases (NIII, LC, MON, MaON, SRF, IMRF, ganglionic cerebellar layer) beta(2)-ARs were colocalized with alpha(2A)-ARs in the same neuron, suggesting their interaction for mediating the physiological functions of nor/adrenaline. Moderate to low labeling of beta(2)-ARs was found in neurons in dorsal telencephalic area, optic tectum (TeO), torus semicircularis (TS), and periventricular gray zone of optic tectum (PGZ). In addition to neuronal, glial expression of beta(2)-ARs was found in astrocytic fibers located in the central gray and dorsal rhombencephalic midline, in close relation to the ventricle. The autoradiographic and immunohistochemical distribution pattern of beta(2)-ARs in the adult zebrafish brain further support the conserved profile of adrenergic/noradrenergic system through vertebrate brain evolution.

Postnatal Development of the Central Nervous System: Anomalies in the Formation of Cerebellum Fissures

A natural defect in rat cerebellum postnatal development has been found in the fissura prima, consisting in various complex configurations of the cerebellar layers. We investigated the genesis of fissure malformations through immunoreactions for PCNA, GFAP, GABAA alpha6, and calbindin to label proliferating cells of the external granular layer (egl), radial glial fibers, mature granule cells, and Purkinje cells, respectively. Results on critical stages of rat postnatal development provided interesting evidences on how the malformation develops in fissures prima and secunda. Early (postnatal day 10) at the site of malformation, the Bergmann radial glia was often retracted and showed distortions and irregular running. The interruption of GFAP-positive radial glial fibers could fit in with the presence of clusters of PCNA-unlabeled cells in the sites of fusion of the egl; the clusters of cells are granule cells since their soma is labeled by GABAA alpha6. Moreover, an altered migration of granule cell precursors to the internal granular layer was evident which, in turn, affected Purkinje cell differentiation and the growth of their dendrites. In summary, the changed relationship among glial fiber morphology, granule cell migration, and Purkinje cell differentiation suggests how the Bergmann glial fibers have a basic role in the foliation process, being the driving physical force in directing migration of the granule cells at the base of fissure.

The Effect of Low Electromagnetic Field in the Cerebellar Layers of Mice

The Effect of Low Electromagnetic Field in the Cerebellar Layers of Mice

On the origin of the MR image phase contrast: An in vivo MR microscopy study of the rat brain at 14.1 T

Recent studies at high magnetic fields using the phase of gradient-echo MR images have shown the ability to unveil cortical substructure in the human brain. To investigate the contrast mechanisms in phase imaging, this study extends, for the first time, phase imaging to the rodent brain. Using a 14.1 T horizontal bore animal MRI scanner for in vivo micro-imaging, images with an in-plane resolution of 33 μm were acquired.Phase images revealed, often more clearly than the corresponding magnitude images, hippocampal fields, cortical layers (e.g. layer 4), cerebellar layers (molecular and granule cell layers) and small white matter structures present in the striatum and septal nucleus. The contrast of the phase images depended in part on the orientation of anatomical structures relative to the magnetic field, consistent with bulk susceptibility variations between tissues. This was found not only for vessels, but also for white matter structures, such as the anterior commissure, and cortical layers in the cerebellum.Such susceptibility changes could result from variable blood volume. However, when the deoxyhemoglobin content was reduced by increasing cerebral blood flow (CBF) with a carbogen breathing challenge, contrast between white and gray matter and cortical layers was not affected, suggesting that tissue cerebral blood volume (and therefore deoxyhemoglobin) is not a major source of the tissue phase contrast.We conclude that phase variations in gradient-echo images are likely due to susceptibility shifts of non-vascular origin.

AUF1 and Hu proteins in the developing rat brain: Implication in the proliferation and differentiation of neural progenitors

Posttranscriptional events such as RNA stabilization are important for cell differentiation, but little is known about the impact of AU-rich binding proteins (AUBPs) on the fate of neural cells. Expression of destabilizing AUBPs such as AUF1 and neuronal-specific stabilizing proteins such as HuB, HuC and HuD was therefore analyzed in the developing central nervous system. Real-time RT-PCR indicated a specific developmental pattern in the postnatal cerebellum, with a progressive down-regulation of AUF1 from P1, whereas HuB was strongly up-regulated at about P7. These changes were accompanied by a progressive increase in AUF1p45 and the disappearance of one HuB isoform from P15, suggesting particular roles for these AUBPs in the developing cerebellum. AUF1 was detected in the three main cerebellar layers, whereas Hu proteins were found only in postmitotic neurons. A role for Hu proteins in the early stages of neuronal differentiation is further supported by arrest of cell proliferation following induction of HuB or HuD expression in a neural stem cell line. The decrease in nestin expression suggest that HuD, but not HuB, favors the transition of neural progenitors into early neuroblasts, but other factors are most probably required for their full differentiation into neurons, insofar as GAP-43 was not detected in HuD-transfected cells. These data suggest critical roles for HuB at the very earliest stages of neuronal differentiation, such as cell cycle exit, and HuD might also be involved in the transition of neural progenitors into early neuroblasts. Taken together, the present results strengthen the importance of AUBPs in brain ontogenesis.

Genesis of Neuronal and Glial Progenitors in the Cerebellar Cortex of Peripuberal and Adult Rabbits

Adult neurogenesis in mammals is restricted to some brain regions, in contrast with other vertebrates in which the genesis of new neurons is more widespread in different areas of the nervous system. In the mammalian cerebellum, neurogenesis is thought to be limited to the early postnatal period, coinciding with end of the granule cell genesis and disappearance of the external granule cell layer (EGL). We recently showed that in the rabbit cerebellum the EGL is replaced by a proliferative layer called ‘subpial layer’ (SPL) which persists beyond puberty on the cerebellar surface. Here we investigated what happens in the cerebellar cortex of peripuberal rabbits by using endogenous and exogenously-administered cell proliferation antigens in association with a cohort of typical markers for neurogenesis. We show that cortical cell progenitors extensively continue to be generated herein. Surprisingly, this neurogenic process continues to a lesser extent in the adult, even in the absence of a proliferative SPL. We describe two populations of newly generated cells, involving neuronal cells and multipolar, glia-like cells. The genesis of neuronal precursors is restricted to the molecular layer, giving rise to cells immunoreactive for GABA, and for the transcription factor Pax2, a marker for GABAergic cerebellar interneuronal precursors of neuroepithelial origin that ascend through the white matter during early postnatal development. The multipolar cells are Map5+, contain Olig2 and Sox2 transcription factors, and are detectable in all cerebellar layers. Some dividing Sox2+ cells are Bergmann glia cells. All the cortical newly generated cells are independent from the SPL and from granule cell genesis, the latter ending before puberty. This study reveals that adult cerebellar neurogenesis can exist in some mammals. Since rabbits have a longer lifespan than rodents, the protracted neurogenesis within its cerebellar parenchyma could be a suitable model for studying adult nervous tissue permissiveness in mammals.

Distribution of ADP-ribosylation factor-related protein 1 in mouse brain.

ADP-ribosylation factor (Arf)-related protein 1 (ARFRP1) is a membrane-associated GTPase, which inhibits the Arf/Sec7-dependent activation of phospholipase D and belongs to the Arf-like (Arl) GTPases. Although ARFRP1 is involved in post-Golgi membrane trafficking and its lack leads to embryonic lethality, little is known about its possible function in the central nervous system. To obtain more knowledge about ARFRP1, we have characterized its mRNA distribution in adult mouse brain by in situ hybridization and real-time PCR. We observed a widespread distribution of ARFRP1-mRNA, with the highest levels in cerebral cortex, thalamic nuclei, colliculus, substantia nigra and granule cell layer of cerebellum. Moderate levels were observed in some amygdaloid nuclei, CA2 area and dentate gyrus of hippocampus, endopiriform nuclei, globus pallidus, striatum, molecular layer of cerebellum, and locus coeruleus, whereas no expression was detected in hypothalamic nuclei, CA1 and CA3 areas of hippocampus, zona incerta. A significant decrease of ARFRP1-mRNA was observed in cerebral cortex following sleep deprivation, whereas no change was observed in cerebellar cortex, locus courelus, brainstem, hippocampus and pontine nuclei. This study provides the first detailed analysis of the regional distribution of ARFRP1 in the mouse brain and a quantitative view of its changes following sleep deprivation.

HP1α guides neuronal fate by timing E2F-targeted genes silencing during terminal differentiation

A critical step of neuronal terminal differentiation is the permanent withdrawal from the cell cycle that requires the silencing of genes that drive mitosis. Here, we describe that the alpha isoform of the heterochromatin protein 1 (HP1) protein family exerts such silencing on several E2F-targeted genes. Among the different isoforms, HP1alpha levels progressively increase throughout differentiation and take over HP1gamma binding on E2F sites in mature neurons. When overexpressed, only HP1alpha is able to ensure a timed repression of E2F genes. Specific inhibition of HP1alpha expression drives neuronal progenitors either towards death or cell cycle progression, yet preventing the expression of the neuronal marker microtubule-associated protein 2. Furthermore, we provide evidence that this mechanism occurs in cerebellar granule neurons in vivo, during the postnatal development of the cerebellum. Finally, our results suggest that E2F-targeted genes are packaged into higher-order chromatin structures in mature neurons relative to neuroblasts, likely reflecting a transition from a 'repressed' versus 'silenced' status of these genes. Together, these data present new epigenetic regulations orchestrated by HP1 isoforms, critical for permanent cell cycle exit during neuronal differentiation.

P2Y1receptor switches to neurons from glia in juvenile versus neonatal rat cerebellar cortex

BackgroundIn the CNS, several P2 receptors for extracellular nucleotides are identified on neurons and glial cells to participate to neuron-neuron, glia-glia and glia-neuron communication.ResultsIn this work, we describe the cellular and subcellular presence of metabotropic P2Y1 receptor in rat cerebellum at two distinct developmental ages, by means of immunofluorescence-confocal and electron microscopy as well as western blotting and direct membrane separation techniques. At postnatal day 21, we find that P2Y1 receptor in addition to Purkinje neurons, is abundant on neuronal specializations identified as noradrenergic by anatomical, morphological and biochemical features. P2Y1 receptor immunoreactivity colocalizes with dopamine β-hydroxylase, tyrosine hydroxylase, neurofilament light chain, synaptophysin and flotillin, but not with glial fibrillary acidic protein for astrocytes. P2Y1 receptor is found enriched in membrane microdomains such as lipid rafts, in cerebellar synaptic vesicles, and is moreover visualized on synaptic varicosities by electron microscopy analysis. When examined at postnatal day 7, P2Y1 receptor immunoreactivity is instead predominantly expressed only on Bergmann and astroglial cells, as shown by colocalization with glial fibrillary acidic protein rather then neuronal markers. At this age, we moreover identify that P2Y1 receptor-positive Bergmann fibers wrap up doublecortin-positive granule cells stretching along them, while migrating through the cerebellar layers.ConclusionMembrane components including purinergic receptors are already known to mediate cellular contact and aggregation in platelets. Our results suggesting a potential role for P2Y1 protein in cell junction/communication and development, are totally innovative for the CNS.

Monoamine receptors and immature cerebellum cytoarchitecture after cisplatin injury

The experimental model of cisplatin treatment provides the opportunity to identify the precise function of the neurotransmitters in some crucial events of brain development, and their interactions or modulatory roles. The serotonin and noradrenaline monoamines influence the formation of the cerebellar cortex circuitry. In this study we found changes in the expression of the serotonin and noradrenaline receptors after a single injection of cisplatin in 10-day-old rats. The growth of Pc dendrites was early altered in lobules VI–VIII of cerebellum vermis. In these lobules, at postnatal day (PD) 17, the cisplatin-induced increase of the serotoninergic receptor 5-HT2AR, a factor that inhibits Pc dendrite growth by acting post-synaptically, occurred in all cerebellar layers, suggesting also alteration of granule cell proliferation and migration. The decreased labelling of beta l adrenergic receptor (beta1AR) in the soma of some Pc at PD11 can be correlated with the altered expression of glutamate receptors and GAD65 (glutamic acid decarboxylase) of and on Pc we have previously described [Pisu, M.B., Guioli, S., Conforti, E., Bernocchi, G., 2003. Signal molecules and receptors in the differential development of cerebellum lobules. Acute effects of cisplatin on nitric oxide and glutamate system in Purkinje cell population. Dev. Brain Res. 145, 229–240; Pisu, M.B., Roda, E., Avella, D., Bernocchi, G., 2004. Developmental plasticity of rat cerebellar cortex after cisplatin injury: inhibitory synapses and differentiating Purkinje neurons. Neuroscience 129, 655–664]. Moreover, beta1AR seems to be the key factor in the cerebellar reorganization between PD17 and PD30. The expression of this receptor was maintained in the molecular layer (ML), in particular in the inhibitory interneurons, despite their different distributions. The labelling of 5-HT1AR in the ML areas lacking Pc dendrite branches could contribute to the recovery phase of the cerebellar cytoarchitecture in cisplatin-treated rats. In general these findings should be taken into consideration in therapeutic interventions for developmental CNS disorders with a morphological basis.