OBJECTIVE: To investigate the variations in the expression of voltage-gated sodium (Na_v) channel subunits during development of rat cerebellar Purkinje neurons and their correlation with maturation of electrophysiological characteristics of the neurons. METHODS: We observed the changes in the expression levels of Na_V1.1, 1.2, 1.3 and 1.6 during the development of Purkinje neurons using immunohistochemistry in neonatal (5-7 days after birth), juvenile (12-14 days), adolescent (21-24 days), and adult (42-60 days) SD rats. Using whole-cell patch-clamp technique, we recorded the spontaneous electrical activity of the neurons in ex vivo brain slices of rats of different ages to analyze the changes of electrophysiological characteristics of these neurons during development. RESULTS: The expression of Na_V subunits in rat cerebellar Purkinje neurons showed significant variations during development. Na_V1.1 subunit was highly expressed throughout the developmental stages and increased progressively with age (P < 0.05). Na_V1.2 expression was not detected in the neurons in any of the developmental stages (P > 0.05). The expression level of Na_V1.3 decreased with development and became undetectable after adolescence (P < 0.05). Na_V1.6 expression was not detected during infancy, but increased with further development (P < 0.05). Na_V1.1 and Na_V1.3 were mainly expressed in the early stages of development. With the maturation of the rats, Na_V1.3 expression disappeared and Na_V1.6 expression increased in the neurons. Na_V1.1 and Na_V1.6 were mainly expressed after adolescence. The total Na_V protein level increased gradually with development (P < 0.05) and tended to stabilize after adolescence. The spontaneous frequency and excitability of the Purkinje neurons increased gradually with development and reached the mature levels in adolescence. The developmental expression of Na_V subunits was positively correlated with discharge frequency (r=0.9942, P < 0.05) and negatively correlated with the excitatory threshold of the neurons (r=0.9891, P < 0.05). CONCLUSION The changes in the expression levels of Na_V subunits are correlated with the maturation of high frequency electrophysiological properties of the neurons, suggesting thatmature Na_V subunit expressions is the basis of maturation of electrophysiological characteristics of the neurons.
Rats ; Animals ; Purkinje Cells/physiology* ; Rats, Sprague-Dawley ; Neurons ; Brain ; Sodium/metabolism*

Cerebellar Purkinje cells (PCs) exhibit two types of discharge activities: simple spike (SS) and complex spike (CS). Previous studies found that noradrenaline (NA) can inhibit CS and bidirectionally regulate SS, but the enhancement of NA on SS is overwhelmed by the strong inhibition of excitatory molecular layer interneurons. However, the mechanism underlying the effect of NA on SS discharge frequency is not clear. Therefore, in the present study, we examined the mechanism underlying the increasing effect of NA on SS firing of PC in mouse cerebellar cortex in vivo and in cerebellar slice by cell-attached and whole-cell recording technique and pharmacological methods. GABA_A receptor was blocked by 100 µmol/L picrotoxin in the whole process. In vivo results showed that NA significantly reduced the number of spikelets of spontaneous CS and enhanced the discharge frequency of SS, but did not affect the discharge frequency of CS. In vitro experiments showed that NA reduced the number of CS spikelets and after hyperpolarization potential (AHP) induced by electrical stimulation, and increased the discharge frequency of SS. NA also reduced the amplitude of excitatory postsynaptic current (EPSC) of parallel fiber (PF)-PC and significantly increased the paired-pulse ratio (PPR). Application of yohimbine, an antagonist of α2-adrenergic receptor (AR), completely eliminated the enhancing effect of NA on SS. The α2-AR agonist, UK14304, also increased the frequency of SS. The β-AR blocker, propranolol, did not affect the effects of NA on PC. These results suggest that in the absence of GABA_A receptors, NA could attenuate the synaptic transmission of climbing fiber (CF)-PC via activating α2-AR, inhibit CS activity and reduce AHP, thus enhancing the SS discharge frequency of PC. This result suggests that NA neurons of locus coeruleus can finely regulate PC signal output by regulating CF-PC synaptic transmission.
Action Potentials/physiology* ; Animals ; Cerebellar Cortex/metabolism* ; Cerebellum/metabolism* ; Mice ; Norepinephrine/pharmacology* ; Purkinje Cells/metabolism* ; Receptors, Adrenergic, alpha-2/metabolism* ; Receptors, GABA-A/metabolism*

Sparse labeling of neurons contributes to uncovering their morphology, and rapid expression of a fluorescent protein reduces the experiment range. To achieve the goal of rapid and sparse labeling of neurons in vivo, we established a rapid method for depicting the fine structure of neurons at 24 h post-infection based on a mutant virus-like particle of Semliki Forest virus. Approximately 0.014 fluorescent focus-forming units of the mutant virus-like particle transferred enhanced green fluorescent protein into neurons in vivo, and its affinity for neurons in vivo was stronger than for neurons in vitro and BHK21 (baby hamster kidney) cells. Collectively, the mutant virus-like particle provides a robust and convenient way to reveal the fine structure of neurons and is expected to be a helper virus for combining with other tools to determine their connectivity. Our work adds a new tool to the approaches for rapid and sparse labeling of neurons in vivo.
Animals ; Cells, Cultured ; Gene Expression ; Genetic Vectors ; genetics ; metabolism ; Green Fluorescent Proteins ; genetics ; metabolism ; Immunohistochemistry ; methods ; Male ; Mice, Inbred C57BL ; Microscopy, Fluorescence ; methods ; Neurons ; cytology ; metabolism ; Purkinje Cells ; cytology ; metabolism ; Semliki forest virus ; genetics

There have been several reports of patients with isolated lesions of the cerebellar vermis presenting with clinical features similar to those of peripheral vestibulopathy. We report a case of small, isolated hematoma in the cerebellar vermis in a patient who presented with vertigo, ipsilesional nystagmus, and body lateropulsion to the contralesional side without the usual signs or symptoms of cerebellar dysfunction. Although they present with symptoms that mimic those of peripheral vestibulopathy, and brain computed tomography shows no abnormality, as there may be a small, isolated hematoma or infarction in the cerebellar vermis. Thus, brain magnetic resonance imaging should be performed in elderly patients with vascular risk factors.
Aged ; Brain ; Cerebellar Diseases ; Cerebellar Vermis ; Hematoma ; Hemorrhage ; Humans ; Infarction ; Magnetic Resonance Imaging ; Risk Factors ; Vertigo

PURPOSE: To investigate regional cerebral amyloid beta retention in cognitively normal Korean adults using F-18 florbetaben (FBB).METHODS: We prospectively analyzed F-18 FBB positron emission tomography (PET)/CT scans of 30 cognitively healthy adults (age range, 50??0 years) using automated quantification. The standardized uptake value ratios (SUVRs) of F-18 FBB were calculated for predefined regions by normalizing the regional count with cerebellar cortex.RESULTS: The distribution of amyloid beta for each brain region revealed no age-related trends (p > 0.05). From all subjects, mean SUVR of amyloid deposit was 1.30 ± 0.18. The right parietal lobe showed the highest SUVR value (1.46 ± 0.23), whereas the right frontal lobe and left precuneus showed the lowest SUVR (1.23 ± 0.25).CONCLUSIONS: We provide reference values of normative data obtained from healthy elderly Koreans and suggest its use for accurate diagnosis of patients with Alzheimer's disease.
Adult ; Aged ; Alzheimer Disease ; Amyloid ; Brain ; Cerebellar Cortex ; Diagnosis ; Frontal Lobe ; Humans ; Parietal Lobe ; Plaque, Amyloid ; Positron-Emission Tomography ; Prospective Studies ; Reference Values

Anaphylaxis usually develop immediately after wasp sting, but may develop even after few days later. Neurological complications after stings are uncommon, although several cases have been reported involving central and/or peripheral nervous system. Although wasp sting-induced encephalitis has been rarely reported, all reported cases showed mental change and severe neurological deterioration. Herein, we report an atypical case who showed biphasic anaphylaxis and delayed-onset cerebellar ataxia following a wasp sting, characterized by mild cerebellar ataxia and excellent response to corticosteroids.
Adrenal Cortex Hormones ; Anaphylaxis ; Bites and Stings ; Cerebellar Ataxia ; Encephalitis ; Peripheral Nervous System ; Wasps

We reviewed the anatomical characteristics of the conduction system in the ventricles of human and ungulate hearts and then raised some questions to be answered by clinical and anatomical studies in the future. The ventricular conduction system is a 3-dimensional structure as compared to the 2-dimensional character of the atrial conduction system. The proximal part consisting of the atrioventricular node, the bundle of His and fascicles are groups of conducting cells surrounded by fibrous connective tissue so as to insulate from the underlying myocardium. Their location and morphological characters are well established. The bundle of His is a cord like structure but the left and right fascicles are broad at the proximal and branching at the distal part. The more distal part of fascicles and Purkinje system are linear networks of conducting cells at the immediate subendocardium but the intra-mural network is detected at the inner half of the ventricular wall. The papillary muscle also harbors Purkinje system not in the deeper part. It is hard to recognize histologically in human hearts but conducting cells as well as Purkinje cells are easily recognized in ungulate hearts. Further observation on human and ungulate hearts with myocardial infarct, we could find preserved Purkinje system at the subendocardium in contrast to the damaged system at the deeper myocardium. Further studies are necessary on the anatomical characteristics of this peripheral conduction system so as to correlate the clinical data on hearts with ventricular arrhythmias.
Arrhythmias, Cardiac ; Atrioventricular Node ; Bundle of His ; Connective Tissue ; Heart ; Heart Conduction System ; Humans ; Myocardial Infarction ; Myocardium ; Papillary Muscles ; Purkinje Cells ; Purkinje Fibers ; Tachycardia, Ventricular

The investigation of the embryonic development of the cerebellum has a long history. The postnatal normal development of the cerebellum in rodents and other animals became a popular topic for morphological investigations nearly a century ago. However, surprisingly, only a few studies are available regarding the prenatal normal development of the rodent cerebellum, especially in guinea pigs. Cell proliferation is essential for the development of the nervous system. The assessment of cell proliferation can be achieved by using various methods. In this study, we investigated the cell proliferation of the cerebellar cortex in guinea pigs at different stages of pregnancy and in postnatal life. Fetuses were obtained by cesarean section at 50 or 60 days of gestation (dg). Immunohistochemistry was performed with proliferating cell nuclear antigen (PCNA) antibody in the cerebellum. Strong PCNA immunoreactivity was observed in the external granular layer (EGL), which is a neurogenic zone in the cerebellum. The proportion of PCNA-IR cells was greater at 1 week than at 60 dg in lobule I, but not lobule VIII. After 50 dg, the width of the EGL continued to decline until 1 week, due to the maturation of the EGL cells. These results demonstrate the pattern of PCNA immunoreactivity in the developing cerebellum of guinea pigs. This serves as a guideline to study abnormal cerebellum development.
Animals ; Cell Proliferation ; Cerebellar Cortex ; Cerebellum ; Cesarean Section ; Embryonic Development ; Female ; Fetus ; Guinea Pigs ; Guinea ; Immunohistochemistry ; Neocortex ; Nervous System ; Pregnancy ; Proliferating Cell Nuclear Antigen ; Rodentia

OBJECTIVE: Propofol is an intravenously administered anesthetic that enhances γ-aminobutyric acid-mediated inhibition in the central nerve system. Other mechanisms may also be involved in general anesthesia. Propofol has been implicated in movement disorders. The cerebellum is important for motor coordination and motor learning. The aim of the present study was to investigate the propofol effect on excitatory synaptic transmissions in cerebellar cortex. METHODS: Excitatory postsynaptic currents by parallel fiber stimulation and complex spikes by climbing fiber stimulation were monitored in Purkinje cells of Wister rat cerebellar slice using whole-cell patch-clamp techniques. RESULTS: Decay time, rise time and amplitude of excitatory postsynaptic currents at parallel fiber Purkinje cell synapses and area of complex spikes at climbing fiber Purkinje cell synapses were significantly increased by propofol administration. CONCLUSION: The detected changes of glutamatergic synaptic transmission in cerebellar Purkinje cell, which determine cerebellar motor output, could explain cerebellar mechanism of motor deficits induced by propofol.
Anesthesia, General ; Anesthetics ; Animals ; Cerebellar Cortex ; Cerebellum ; Excitatory Postsynaptic Potentials ; Learning ; Movement Disorders ; Patch-Clamp Techniques ; Propofol* ; Purkinje Cells* ; Rats ; Synapses ; Synaptic Transmission

What is memory? How does the brain process the sensory information and modify an organism's behavior? Many neuroscientists have focused on the activity- and experience-dependent modifications of synaptic functions in order to solve these fundamental questions in neuroscience. Recently, the plasticity of intrinsic excitability (called intrinsic plasticity) has emerged as an important element for information processing and storage in the brain. As the cerebellar Purkinje cells are the sole output neurons in the cerebellar cortex and the information is conveyed from a neuron to its relay neurons by forms of action potential firing, the modulation of the intrinsic firing activity may play a critical role in the cerebellar learning. Many voltage-gated and/or Ca²⁺-activated ion channels are involved in shaping the spiking output as well as integrating synaptic inputs to finely tune the cerebellar output. Recent studies suggested that the modulation of the intrinsic excitability and its plasticity in the cerebellar Purkinje cells might function as an integrator for information processing and memory formation. Moreover, the intrinsic plasticity might also determine the strength of connectivity to the sub-cortical areas such as deep cerebellar nuclei and vestibular nuclei to trigger the consolidation of the cerebellar-dependent memory by transferring the information.
Action Potentials ; Automatic Data Processing ; Brain ; Cerebellar Cortex ; Cerebellar Nuclei ; Cerebellum ; Fires ; Ion Channels ; Learning* ; Memory ; Neuronal Plasticity ; Neurons ; Neurosciences ; Plastics* ; Purkinje Cells* ; Vestibular Nuclei