Inverted pyramidal neurons and their axons in the neocortex of reeler mutant mice

Summary Inverted pyramidal neurons are very abundant in the cerebral cortex of the adult reeler mutant mouse. Two types of inverted pyramid are found in rapid Golgi impregnations. In the first type the axon starts from the base of the cell body and bends towards the white matter. In the second type, which is more common, the axon emerges from the apical dendritic tree and descends directly towards the white matter.Despite its abnormal topography, the site of origin of the axon in pyramids of the second type displays a normal differentiation, when analysed with the electron microscopic Golgi technique, suggesting that the ectopic initial axon segment is able to fulfil its normal functions.     

Passive cable properties of hippocampal CA3 pyramidal neurons

The passive electrical cable properties of CA3 pyramidal neurons from guinea pig hippocampal slices were investigated by applying current steps and recording the voltage transients from 25 CA3 neurons, using a single intracellular microelectrode and a 3-kHz time-share system. Two independent methods were used for estimating the equivalent electrotonic length of the dendrites, L, and the dendritic to somatic conductance ratio, . The first method is similar to that used by Gorman and Mirolli (1972) and gave an average L of 0.96; the average was 2.44. The second method is derived here for the first time and assumes a finite-length cable with lumped soma. It is an exact solution for L and , using the slopes and intercepts of the first two peeled exponentials. The average L was 0.94; the average was 1.51. The results, using both methods, are in close agreement. The average membrane time constant for all 25 CA3 neurons was 23.6 ms, suggesting a large (23,600 cm²) average membrane resistivity. It is concluded that CA3 neurons are electronically short.This work was supported by Grants NS 11535 and NS 15772 from the National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, U.S. Public Health Service.     

Cholinergic pyramidal neurons of the motor region of human neocortex

By means of histochemical methods for revealing +choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) cytoarchitectonic of the field 4 of the motor cortex of the cerebrum has been studied in 5 persons at the age of 33-65 years. An essential part of neurons at revealing AChE and most of them at revealing ChAT do not react. Among giant pyramidal neurons (Bets) according to ChAT activity, 4 types are distinguished: neurons with low, middle, high and very high activity. The presence of ChAT is ascertained in middle and large pyramidal neurons of the III layer. Presence of ChAT-positive synapses is demonstrated in apical dendrites. A conclusion is made that less part of the pyramidal in the III, V layers are cholinergic ones.     

Endogenous nature of spontaneous bursting in hippocampal pyramidal neurons

The normal spontaneous bursting behavior of hippocampal pyramidal neurons was investigated. Bursting frequency was found to be membrane potential dependent, the frequency increasing with maintained depolarization and decreasing upon hyperpolarization. Short depolarizing-current pulses would trigger bursts which outlasted the stimulus, and bursting continued when synaptic transmission had been blocked. The spontaneous bursts of these neurons, in contrast to bursts induced by convulsive agents, appear to exhibit the classical behavior of endogenous bursts as observed in invertebrate neurons. The endogenous bursts in hippocampal neurons may result, also, from an interplay of intrinsic membrane currents.     

Postnatal morphological changes in neurons and glial cells in neocortex of mice developing at the background of serotonin deficit

It has been shown that deficit of serotonin during embryogenesis in rodents is accompanied by changes of morphological characteristics of neurons and glial cells at the period of postnatal development. A characteristic peculiarity of these changes is cell vacuolization that is of different expression in various cortical layers. In the experimental animals as compared with control ones, neurons of all neocortex layers have changed nuclei and a reduced volume of the cytoplasm. In neurons of upper layers, nuclei and cytoplasm contain occasional small vacuoles. In deep layers, vacuolization both of nuclei and of the cytoplasm is expressed to the much greater degree and vacuoles of large size are predominant. Results of immunocytochemical study have shown that in animals developing at the background of serotonin deficit there takes place a delay of the rates of formation and differentiation of astrocytic glia.     

Synaptic properties of layer VI inverted pyramidal cells in the rodent somatosensory cortex

The properties of specific cortical cell types enable greater understanding of how cortical microcircuits process and transmit sensory, motor, and cognitive information. Previous reports have characterized the intrinsic properties of the inverted pyramidal cell (IPC) where the most prominent dendrite is orientated towards the cortical white matter. Using whole cell patch clamp recordings from rat and mouse somatosensory cortex in conjunction with electric microstimulation of the white matter we characterized the synaptic inputs onto IPCs and the more common upright pyramidal cell (UPC) in the infragranular layers. Both classes of pyramidal cells received monosynaptic glutamatergic input following white matter stimulation, but varied on a number of parameters. Most prominently, UPCs displayed higher amplitude responses and showed greater rates of depression compared to IPCs. These data reinforce the view that IPCs are a separate functional class of cortical neuron.     

Effect of cannabinoids on glycine-activated currents in pyramidal neurons of the rat hippocampus

Using electrophysiological techniques (a patch-clamp technique in the whole-cell configuration and intracellular perfusion of neurons), we studied the effect of cannabinoids on the characteristics of glycine-activated currents in freshly isolated pyramidal neurons of the rat hippocampus. We found that endocannabinoids (anandamide and 2-arachidonoyl glycerol), as well as a synthetic cannabinoid, WIN 55,212-2, when applied in physiological concentrations, decreased the amplitude of glycine-activated currents. The agents under study accelerated the kinetics of activation and desensitization of glycine-induced Cl⁻ currents. The characteristics of the currents recovered after washout from cannabinoids. Changes in the kinetics of desensitization of glycine-activated currents depended noticeably on the holding potential; at positive potentials the sensitivity to cannabinoids was higher. These effects of cannabinoids were also observed in the presence of antagonists of CB1/CB3 receptors and an inhibitor of G proteins, GDPβS. These data indicate that under our experimental conditions cannabinoids exerted direct effects on glycine receptors. Neirofiziologiya/Neurophysiology, Vol. 39, No. 1, pp. 15–21, January–February, 2007.     

人离体新皮层神经元的神经生物学特性

活检得到的人离体新皮层神经元的神经生物学研究表明,人新皮层神经元包括快锋电位和规则锋电位两种细胞类型,并存在局部抑制性突触环路和局部兴奋性突触环路,以兴奋性和抑制性氨基酸为重要的神经递质。另外,神经元的神经生物学特性还与胞外钙镁离子浓度有关。     

M-channels modulate the intrinsic excitability and synaptic responses of layer 2/3 pyramidal neurons in auditory cortex

Neurons in the auditory cortex are believed to utilize temporal patterns of neural activity to accurately process auditory information but the intrinsic neuronal mechanism underlying the control of auditory neural activity is not known. The slowly activating, persistent K⁺ channel, also called M-channel that belongs to the Kv7 family, is already known to be important in regulating subthreshold neural excitability and synaptic summation in neocortical and hippocampal pyramidal neurons. However, its functional role in the primary auditory cortex (A1) has never been characterized. In this study, we investigated the roles of M-channels on neuronal excitability, short-term plasticity, and synaptic summation of A1 layer 2/3 regular spiking pyramidal neurons with whole-cell current-clamp recordings in vitro. We found that blocking M-channels with a selective M-channel blocker, XE991, significantly increased neural excitability of A1 layer 2/3 pyramidal neurons. Furthermore, M-channels controled synaptic responses of intralaminar-evoked excitatory postsynaptic potentials (EPSPs); XE991 significantly increased EPSP amplitude, decreased the rate of short-term depression, and increased the synaptic summation. These results suggest that M-channels are involved in controlling spike output patterns and synaptic responses of A1 layer 2/3 pyramidal neurons, which would have important implications in auditory information processing.     

Somatodendritic localization of Translin, a component of the Translin/Trax RNA binding complex

Recent studies implicating dendritic protein synthesis in synaptic plasticity have focused attention on identifying components of the molecular machinery involved in processing dendritic RNA. Although Translin was originally identified as a protein capable of binding single-stranded DNA, subsequent studies have demonstrated that it also binds RNA in vitro. Because previous studies indicated that Translin-containing RNA/single-stranded DNA binding complexes are highly enriched in brain, we and others have proposed that it may be involved in dendritic RNA processing. To assess this possibility, we have conducted studies aimed at defining the localization of Translin and its partner protein, Trax, in brain. In situ hybridization studies demonstrated that both Translin and Trax are expressed in neurons with prominent staining apparent in cerebellar Purkinje cells and neuronal layers of the hippocampus. Subcellular fractionation studies demonstrated that both Translin and Trax are highly enriched in the cytoplasmic fraction compared with nuclear extracts. Furthermore, immunohistochemical studies with Translin antibodies revealed prominent staining in Purkinje neuron cell bodies that extends into proximal and distal dendrites. A similar pattern of somatodendritic localization was observed in hippocampal and neocortical pyramidal neurons. These findings demonstrate that Translin is expressed in neuronal dendrites and therefore support the hypothesis that the Translin/Trax complex may be involved in dendritic RNA processing.     

P物质抑制培养大鼠海马大锥体细胞GABA-激活电流

研究主要探讨P物质（SP）对GABA－激活电流的调制。实验在培养的新生大鼠海马大锥体细胞上进行。应用全细胞膜片箝技术记录GABA激活的内向电流。在被检的大锥体细胞中,有72％（66／92）的神经元对GABA和SP同时敏感,预后SP后,GABA激活电流明显地被抑制,此抑制作用是呈剂量依赖性的。在预加10^-8,10^-7,10^-6,10^-5mol/LSP后,GABA的激活电流分别降低18％,24．8％,25．9％和28％,用SP的拮抗剂 spantide能阻断此种抑制作用,在电极中灌注H7（PKC抑制剂）能取消此抑制作用,上述结果提示：SP对GABA激活电流的抑制作用是SP作用于SP受体,通过胞内第二信使,使GABAA受体通道复合体胞内磷酸化所致。     

5-HT<Subscript>1A</Subscript> receptor expression in pyramidal neurons of cortical and limbic brain regions

We studied expression of the 5-HT_1A receptor in cortical and limbic areas of the brain of the tree shrew. In situ hybridization with a receptor-specific probe and immunocytochemistry with various antibodies was used to identify distinct neurons expressing the receptor. In vitro receptor autoradiography with ³H-8-OH-DPAT (³H-8-hydroxy-2-[di-n-propylamino]tetralin) was performed to visualize receptor-binding sites. In the prefrontal, insular, and occipital cortex, 5-HT_1A receptor mRNA was expressed in pyramidal neurons of layer 2, whereas ³H-8-OH-DPAT labeled layers 1 and 2 generating a columnar-like pattern in the prefrontal and occipital cortex. In the striate and ventral occipital cortex, receptor mRNA was present within layers 5 and 6 in pyramidal neurons and Meynert cells. Pyramid-like neurons in the claustrum and anterior olfactory nucleus also expressed the receptor. Principal neurons in hippocampal region CA1 expressed 5-HT_1A receptor mRNA, and ³H-8-OH-DPAT labeled both the stratum oriens and stratum radiatum. CA3 pyramidal neurons displayed low 5-HT_1A receptor expression, whereas granule neurons in the dentate gyrus revealed moderate expression of this receptor. In the amygdala, large pyramid-like neurons in the basal magnocellular nucleus strongly expressed the receptor. Immunocytochemistry with antibodies against parvalbumin, calbindin, and gamma aminobutyric acid (GABA) provided no evidence for 5-HT_1A receptor expression in GABAergic neurons in cortical and limbic brain areas. Our data agree with previous findings showing that the 5-HT_1A receptor mediates the modulation of glutamatergic neurons. Expression in the limbic and cortical areas suggested an involvement of 5-HT_1A receptors in emotional and cognitive processes.This work was supported by the German Science Foundation (SFB 406; C4 to G.F.).     

结构函数的标度律

分析了GOY模型结构函数的标度律．指出结构函数的振荡涨落导致非线性标度律。     

Initiation of Sodium Spikelets in Basal Dendrites of Neocortical Pyramidal Neurons

Cortical information processing relies critically on the processing of electrical signals in pyramidal neurons. Electrical transients mainly arise when excitatory synaptic inputs impinge upon distal dendritic regions. To study the dendritic aspect of synaptic integration one must record electrical signals in distal dendrites. Since thin dendritic branches, such as oblique and basal dendrites, do not support routine glass electrode measurements, we turned our effort towards voltage-sensitive dye recordings. Using the optical imaging approach we found and reported previously that basal dendrites of neocortical pyramidal neurons show an elaborate repertoire of electrical signals, including backpropagating action potentials and glutamate-evoked plateau potentials. Here we report a novel form of electrical signal, qualitatively and quantitatively different from backpropagating action potentials and dendritic plateau potentials. Strong glutamatergic stimulation of an individual basal dendrite is capable of triggering a fast spike, which precedes the dendritic plateau potential. The amplitude of the fast initial spikelet was actually smaller that the amplitude of the backpropagating action potential in the same dendritic segment. Therefore, the fast initial spike was dubbed “spikelet”. Both the basal spikelet and plateau potential propagate decrementally towards the cell body, where they are reflected in the somatic whole-cell recordings. The low incidence of basal spikelets in the somatic intracellular recordings and the impact of basal spikelets on soma-axon action potential initiation are discussed.     

Serotoninergic modulation of GABAergic synaptic transmission in developing rat CA3 pyramidal neurons

Serotoninergic modulation of GABAergic mIPSCs was investigated in immature (postnatal 12–16-days old) rat CA3 pyramidal neurons using a conventional whole-cell patch clamp technique. Serotonin or 5-hydroxytryptamine (5-HT) (10 μmol/L) transiently and explosively increased mIPSC frequency with a small increase in the current amplitude. However, 5-HT did not affect the GABA-induced postsynaptic currents, indicating that 5-HT acts presynaptically to facilitate the probability of spontaneous GABA release. The 5-HT action on GABAergic mIPSC frequency was completely blocked by 100 nmol/L MDL72222, a selective 5-HT₃ receptor antagonist, and mimicked by mCPBG, a selective 5-HT₃ receptor agonist. The 5-HT action on GABAergic mIPSC frequency was completely occluded either in the presence of 200 μmol/L Cd²⁺ or in the Na⁺-free external solution, suggesting that the 5-HT₃ receptor-mediated facilitation of mIPSC frequency requires a Ca²⁺influx passing through voltage-dependent Ca²⁺channels from the extracellular space, and that presynaptic 5-HT₃ receptors are less permeable to Ca²⁺. The 5-HT action on mIPSC frequency in the absence or presence of extracellular Na⁺ gradually increased with postnatal development. Such a developmental change in the 5-HT₃ receptor-mediated facilitation of GABAergic transmission would play important roles in the regulation of excitability as well as development in CA3 pyramidal neurons.     

The development of peptide-containing neurons within neocortical transplants in adult mice

Transplantation of embryonic neocortex into adult host neocortex leads to the survival of many donor cells, with the subsequent differentiation of the cortical neurons within a loosely laminated cellular pattern. We wanted to know whether peptide-containing neurons that are known to exist in normal neocortex would survive in the transplants, and if so, whether they would differentiate into morphological cell types that normally contain these peptides in cortex. By 30 days after transplantation, the implants were well vascularized and the donor neurons appeared healthy in Nissl-stained preparations. AChE-positive axons grew across the interface and innervated the transplant in moderate densities. Immunocytochemical localization of peptides in the transplant revealed that processes containing the four peptides normally present in cortex also develop in the transplants. These were vasoactive intestinal polypeptide, cholecystokinin, pancreatic polypeptide and somatostatin. Other peptides not yet demonstrated in and presumably not present in neocortex, did not develop in the transplants. These included alpha-melanocyte stimulating hormone, arginine-vasopressin, corticotropin releasing factor, beta-endorphin and substance P. The results demonstrate that peptide-immunoreactive neurons survive in neural transplants, where they develop complicated patterns of axonal arborization. The conditions used in these experiments produced no evidence that peptidergic neurons within the transplant grow out of the transplant and into the host brain within six weeks. Similarly, host peptidergic axons were never seen crossing the interface zone and entering the transplant in any significant numbers.     

Prenatal stress on the kinetic properties of Ca2+ and K+ channels in offspring hippocampal CA3 pyramidal neurons

Prenatal stress is known to cause neuronal loss and oxidative damage in the hippocampus of offspring rats. To further understand the mechanisms, the present study was undertaken to investigate the effects of prenatal stress on the kinetic properties of high-voltage-activated (HVA) Ca(2+) and K(+) channels in freshly isolated hippocampal CA3 pyramidal neurons of offspring rats. Pregnant rats in the prenatal stress group were exposed to restraint stress on days 14-20 of pregnancy three times daily for 45 min. The patch clamp technique was employed to record HVA Ca(2+) and K(+) channel currents. Prenatal stress significantly increased HVA Ca(2+) channel disturbance including the maximal average HVA calcium peak current amplitude (-576.52+/-7.03 pA in control group and -702.05+/-6.82 pA in prenatal stress group, p<0.01), the maximal average HVA Ca(2+) current density (-40.89+/-0.31 pA/pF in control group and -49.44+/-0.37 pA/pF in prenatal stress group, p<0.01), and the maximal average integral current of the HVA Ca(2+) channel (106.81+/-4.20 nA ms in control group and 133.49+/-4.59 nA ms in prenatal stress group, p<0.01). The current-voltage relationship and conductance--voltage relationship of HVA Ca(2+) channels and potassium channels in offspring CA3 neurons were not affected by prenatal stress. These data suggest that exposure of animals to stressful experience during pregnancy can exert effects on calcium ion channels of offspring hippocampal neurons and that the calcium channel disturbance may play a role in prenatal stress-induced neuronal loss and oxidative damage in offspring brain.     

Scaling properties of childhood infectious diseases epidemics before and after mass vaccination in Canada

The goal of this paper is to analyse the scaling properties of childhood infectious disease time-series data. We present a scaling analysis of the distribution of epidemic sizes of measles, rubella, pertussis, and mumps outbreaks in Canada. This application provides a new approach in assessing infectious disease dynamics in a large vaccinated population. An inverse power-law (IPL) distribution function has been fit to the time series of epidemic sizes, and the results assessed against an exponential benchmark model. We have found that the rubella epidemic size distribution and that of measles in highly vaccinated periods follow an IPL. The IPL suggests the presence of a scale-invariant network for these diseases as a result of the heterogeneity of the individual contact rates. By contrast, it was found that pertussis and mumps were characterized by a uniform network of transmission of the exponential type, which suggests homogeneity in the contact rate or, more likely, boiled down heterogeneity by large intermixing in the population. We conclude that the topology of the network of infectious contacts depends on the disease type and its infection rate. It also appears that the socio-demographic structure of the population may play a part (e.g. pattern of contacts according to age) in the structuring of the topology of the network. The findings suggest that there is relevant information hidden in the variation of the common contagious disease time-series data, and that this information can have a bearing on the strategy of vaccination programs.