Segmentation of the response of a neuronal network into clusters with similar activity

An important question in the analysis of the electrical activity of a large population of neurons is the detection of families of neurons having a similar pattern of electrical activity, so that the original neuronal network can be decomposed into distinct clusters. This paper describes how it is possible to segment the activity of a neuronal network into clusters of sites with similar patterns of activity. Such a segmentation gives insight on how the network is organized, on how it functions and on its behavior as a dynamical system. Simulation and experiments on real data suggest that the correct approach to solve these problems must use multiresolution analysis. The method has been applied to both synthetic data and real data coming from a network of dissociated cortical neurons from neonatal rat brain.     

Mapping of the pressure response element of the c-fos gene by direct DNA injection into beating hearts

In vivo gene transfer into various organs of postnatal animals has recently been demonstrated. We applied this technique in order to map the promoter element of the protooncogene c-fos in the myocardium that responds to left ventricular pressure overload in vivo. Beating rat hearts were directly injected with a recombinant plasmid containing a 356-base pair upstream regulatory element of the mouse c-fos gene fused to a reporter gene. Two days after the injection, the hearts were excised and buffer-perfused. Acute pressure overload was applied for 2 h by inflating an intraventricular balloon. Pressure overload increased the myocardial reporter gene activity by 3-8-fold (p < 0.01). Deletion and point mutations in the serum response element (SRE) of the c-fos promoter resulted in loss of pressure-induced reporter gene expression, indicating that the SRE is necessary for pressure response. The SRE alone was sufficient to confer pressure responsiveness to the minimal c-fos promoter, confirming that the pressure response element coincides with the SRE. A construct containing a point mutation at the p62TCF binding site of the SRE did not respond to pressure overload or to a protein kinase C activator but retained responsiveness to a calcium ionophore. This suggests that pressure overload may activate the c-fos promoter by a protein kinase C-dependent pathway. Thus, a directly injected gene can be regulated in the host cells by a physical stimulus to the intact organ. The in vivo DNA injection technique is a useful method to study complex organ physiology at the molecular level.     

FOS is induced by singing in distinct neuronal populations in a motor network

The acute and subacute effects of intracerebroventricularly (ICV) administered nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) on locomotor activity were evaluated in awake adult rats. Immediately after ICV injection through an implanted cannula, locomotor activity was measured by a computerized system using infrared photocells, which allowed us to record locomotion, motility, and rearing simultaneously. A single dose of 5 microg mouse beta-NGF produced significant increases in horizontal ambulatory components of locomotor activity (locomotion and motility), but not vertical movement (rearing) 30-45 min after ICV administration. These increases lasted for at least 3-4 h. Systemic injection of 2.0 mg/kg mecamylamine, a central nicotinic receptor antagonist, inhibited the hyperactivity induced by NGF. Systemic injection of 0.5 mg/kg scopolamine, a muscarinic receptor antagonist, did not interfere with the NGF effects. Thus, while scopolamine induced marked increases in all three measures of behavior in both NGF and cytochrome-c-treated animals, locomotion and motility remained significantly higher in the NGF group. Immunohistochemistry demonstrated that NGF diffused readily from the ventricular space into brain parenchyma on the injected side and could be visualized 1 h after ICV injection. These results suggest that ICV administration of NGF increases locomotor activity by inducing acetylcholine release, and that nicotinic receptors are involved in the hyperactivity induced by NGF. ICV administration of 5 microg recombinant human BDNF had no significant effect on locomotor activity during the 0- to 4-h period after ICV injection. However, it produced significant decreases in locomotion, motility, and rearing 24-26 h later. Hence ICV administration of BDNF has entirely different effects on animal behavior from those evoked by NGF. While NGF elicits increases in ambulatory behavior within hours, BDNF causes delayed decreases in ambulatory behavior.     

The neuronal network of the hippocampus: a morphological analysis

The use of new methods of morphologic analysis made it possible to detail significantly already known insights and to formulate the new ones concerning the hippocampal construction. This review discusses in detail the principles of structural organization of all intrahippocampal interneuronal connections and projections to the hippocampus from entorhinal cortex. Also, other afferent and efferent pathways and connections of polymorphic neurons of hippocampus are studied. Revision of the lamellar principle of hippocampal organization and involvement of inhibitory system in restricting an excitation propagation along the hippocampus is discussed.     

Reconfiguration of the respiratory network at the onset of locust flight

Reconfiguration of the respiratory network at the onset of locust flight. J. Neurophysiol. 80: 3137-3147, 1998. The respiratory interneurons 377, 378, 379 and 576 were identified within the suboesophageal ganglion (SOG) of the locust. Intracellular stimulation of these neurons excited the auxillary muscle 59 (M59), a muscle that is involved in the control of thoracic pumping in the locust. Like M59, these interneurons did not discharge during each respiratory cycle. However, the SOG interneurons were part of the respiratory rhythm generator because brief intracellular stimulation of these interneurons reset the respiratory rhythm and tonic stimulation increased the frequency of respiratory activity. At the onset of flight, the respiratory input into M59 and the SOG interneurons was suppressed, and these neurons discharged in phase with wing depression while abdominal pumping movements remained rhythmically active in phase with the slower respiratory rhythm (Fig. ). The suppression of the respiratory input during flight seems to be mediated by the SOG interneuron 388. This interneuron was tonically activated during flight, and intracellular current injection suppressed the respiratory rhythmic input into M59. We conclude that the respiratory rhythm generator is reconfigured at flight onset. As part of the rhythm-generating network, the interneurons in the SOG are uncoupled from the rest of the respiratory network and discharge in phase with the flight rhythm. Because these SOG interneurons have a strong influence on thoracic pumping, we propose that this neural reconfiguration leads to a behavioral reconfiguration. In the quiescent state, thoracic pumping is coupled to the abdominal pumping movements and has auxillary functions. During flight, thoracic pumping is coupled to the flight rhythm and provides the major ventilatory movements during this energy-demanding locomotor behavior.     

Pro-epileptic changes in synaptic function can be accompanied by pro-epileptic changes in neuronal excitability

Repetitive sensory input, stroboscopic lights or repeated sounds can induce epileptic seizures in susceptible individuals. In order to understand the process we have to consider multiple factors. The output of a set of neurones is determined by the amount of excitatory synaptic input, the degree of positive feedback and their inherent electrical excitability, which can be modified by synaptic inhibition. Recent research has shown that it is possible to separate these phenomena, and that they do not always behave in unison.     

Intrinsic function of a neuronal network - a vertebrate central pattern generator

The cellular bases of vertebrate locomotor behaviour is reviewed using the lamprey as a model system. Forebrain and brainstem cell populations initiate locomotor activity via reticulospinal fibers activating a spinal network comprised of glutamatergic and glycinergic interneurons. The role of different subtypes of Ca2+ channels, Ca2+ dependent K+ channels and voltage dependent NMDA channels at the neuronal and network level is in focus as well as the effects of different metabotropic, aminergic and peptidergic modulators that target these ion channels. This is one of the few vertebrate networks that is understood at a cellular level.     

Tracing prehistoric migrations by the viruses they carry: human T-cell lymphotropic viruses as markers of ethnic relationships

Three reasons that HTLV-I and HTLV-II would not be expected to trace human migrations over extended time periods have been examined, and none has proven fatal to the theory. Transmission of the HTLVs (human T-cell lymphotropic viruses) in endemic settings highly depends on passage through breast milk, and this creates a pattern of distribution similar to that of mitochondrial DNA. The HTLVs probably evolve at variable rates, making the extent of sequence change a poor tool for dating human migrations. However, qualitative relationships between the sequence of human population separations and virus strain may be more regular. The uniqueness of viruses as markers of human relationship gives this method special value as a source of novel ideas regarding human movements and as independent confirmation of migration hypotheses that have been based on more conventional methods.     

A neuronal network for computing population vectors in the leech

The correlation of neuronal activity with sensory input and behavioural output has revealed that information is often encoded in the activity of many neurons across a population, that is, a neural population code is used. The possible algorithms that downstream networks use to read out this population code have been studied by manipulating the activity of a few neurons in a population. We have used this approach to study population coding in a small network underlying the leech local bend, a body bend directed away from a touch stimulus. Because of the small size of this network we are able to monitor and manipulate the complete set of sensory inputs to the network. We show here that the population vector formed by the spike counts of the active mechanosensory neurons is well correlated with bend direction. A model based on the known connectivity of the identified neurons in the local bend network can account for our experimental results, and is suitable for reading out the neural population vector. Thus, for the first time to our knowledge, it is possible to link a proposed algorithm for neural population coding with synaptic and network mechanisms in an experimental system.     

Reflex bronchial vasodilation in dogs evoked by injection of a small volume of water into a bronchus

Injection of water into a lobar bronchus stimulates airway C-fibers and rapidly adapting receptors and evokes airway defense reflexes. To determine whether this stimulus also evokes a reflex increase in bronchial blood flow (Qbr), we injected 1-2 ml of water into a lobar bronchus in anesthetized dogs. Injection decreased arterial pressure but increased Qbr from 9 +/- 1 to 21 +/- 3 ml/min. The increase had a latency of 6-8 s and reached a peak after approximately 20 s; Qbr returned to control after 60-90 s. Airway mucosal blood flow, measured by colored microspheres, increased in proportion to Qbr. In contrast, flow in an adjacent intercostal artery that did not supply the airway decreased slightly. Injection of isosmotic saline had little effect. In 13 of 16 dogs, the water-induced increase in Qbr was abolished by cutting or cooling the cervical vagus nerves and hence was entirely dependent on centrally mediated vagal pathways. When the vagus nerves were intact, about one-third of the vasodilator response remained after pharmacological blockade of muscarinic and adrenergic receptors. We conclude that in dogs the defense response to water in the lower airways includes a large increase in Qbr that is partly due to activation of nonadrenergic noncholinergic autonomic pathways.     

Spinal serotonergic receptors mediate facilitation of a nociceptive reflex by subcutaneous formalin injection into the hindpaw in rats

It is documented that spinal nociceptive transmission receives descending facilitatory and inhibitory modulation from supraspinal structures. The rostral ventral medulla (RVM), including the nucleus raphe magnus (NRM), nuclei reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGCalpha), is the major bulbar relay of descending modulatory influences. Pharmacological studies show that facilitation of a spinal nociceptive tail-flick (TF) reflex induced by stimulation in the NGC and NGCalpha is mediated by spinal serotonergic receptors. The present series of experiments provide evidence that activation of spinal serotonergic systems are critical for both induction and maintenance of secondary hyperalgesia induced by subcutaneous injection of formalin into one hindpaw. Subcutaneous injection of formalin produced facilitation of tail withdrawal (mechanical) and the TF reflex (thermal). Facilitatory effects persisted for at least 30 min. Peripheral blockade of the activity by local injection of a hydrophilic lidocaine derivative (QX-314, 5%) into the injected hindpaw abolished both mechanical and thermal facilitation, indicating that peripheral input is important to maintain long-lasting facilitation. Intrathecal application of a serotonergic receptor antagonist methysergide at a dose (64 nmol) which completely blocked descending facilitation produced by electrical- or chemical-stimulation in the NGC and NGCalpha also significantly attenuated or completely abolished facilitation of tail withdrawal and the TF reflex induced by formalin. Methysergide was effective whether the injection was performed before or after the formalin injection. These results suggest that activation of descending facilitatory serotonergic influences by a prolonged noxious stimulation could contribute to secondary hyperalgesia observed at the tail.     

Effect of intracerebroventricular injection of ramipril on the drinking response caused by injection of noradrenaline into the third ventricle

We studied the effect of ramipril injected into the third ventricle (3rdV) on the control of water intake induced by injection of noradrenaline into the 3rdV of adult male Holtzman rats (250-300 g) implanted with a chronic stainless steel cannula into the 3rdV. The injection volume was always 1 microliter and was injected over a period of 30-60 sec. Control animals were injected with 0.15 M NaCl. After the injection of isotonic saline (control, 0.15 M NaCl) into the 3rdV, water ingestion was 0.3 +/- 0.1 ml/h. Ramipril (1 mircogram/microliter) injected into the 3rdV prior to isotonic saline produced no changes in water ingestion (0.4 +/- 0.2 ml/h). The injection of noradrenaline (40 nmol/microliter) after isotonic saline induced an increase in water intake (3.0 +/- 1.1 ml/h). The prior injection of ramipril decreased this ingestion to 1.8 +/- 0.3 ml/h. These data show that the inhibition of converting enzyme in the brain reduces the water intake induced by catecholaminergic stimulation. We conclude that the brain is able to transform the prodrug ramipril into the active drug ramiprilat.     

Effects of synaptic noise on a neuronal pool model with strong excitatory drive and recurrent inhibition

A model originally proposed by Akazawa and Kato (1990) for the spinal cord was adopted as prototypical of a neuronal pool with strong excitatory drive and strong recurrent inhibition. Our simulations of the model have shown that a strong synchronization occurs between the spike trains in the neuronal pool. This happens because the proposed model has a single and strong excitatory drive on the neuronal pool. However, usually a multitude of other randomly occurring synaptic inputs impinge on the neuronal pool and therefore a new investigation was carried out to study the effects of synaptic noise on the network behavior. The synaptic noise decreased the degree of synchronization of the neuronal spike trains but on the other hand caused an unexpected decrease in the mean firing rate of the neuronal pool. A detailed analysis indicated that this phenomenon is due to a combination of two mechanisms: a saturation of the feedback inhibition and a decrease of the synchronization in the neuronal pool with synaptic noise. The synaptic noise caused a more frequent activation of the saturated recurrent inhibitory feedback loop along time, thereby increasing the inhibitory effect on the neuronal pool.     

Seizure activity and lesions of neuronal cells by intrahippocampal injection of guanidinosuccinic acid in rats]

Intrahippocampal injection(ihci) of guanidinosuccinic acid (GSA) to rats, induced typical generarized clonic seizures and epileptiform discharges in electrohippocampogram (EHG) and electrocorticogram (ECoG), degenerative changes of neuronal cells in the injected side hippocampus. The pyramidal cells in CA1 area were found to be more vulnerable to GSA than the granular cells. Phenobarbital and phenytoin are typical antiepiletics, but in no case did they successfully protect against GSA induced convulsions, epileptiform discharges in the EHG and ECoG and neurolysis. Ketamine, a selective noncompetitive NMDA receptor antagonist, was shown to protect against not only seizures, but also neuronal cell damage induced by GSA. All these results indicate that GSA very like the endogenous excitatory amino acid, glutamic acid, it also has such effects mentioned above. Therefore, the NMDA receptor may mediate both effects of GSA.     

High-pressure injection of air into a peirce-smith copper converter

Plant trials have been conducted at the Tacoma Smelter of ASARCO to assess the effect on tuyere blockage and refractory erosion at the tuyere line, of increasing the injection pressure of air into a Peirce-Smith converter. Four tuyeres each having an ID of 19.1 mm (0.75 inch) were installed toward one end of the tuyere line of the No. 4 converter. Air and oxygen-enriched air were injected at 414 kPag (60 psig) through these tuyeres and at the usual 83 kPag (12 psig) through the remainder of the tuyeres in an otherwise normal converter campaign. The test campaign consisted of 88 charges and lasted for 89 days. During this period, punching of the high-pressure tuyeres was found to be unnecessary; and when, as a precaution, the tuyeres were cleaned by hand at the end of a charge, they were always open. Also, it was observed that the flow of high-pressure air remained constant. Accretion formation around the tip of the high-pressure tuyeres varied from charge to charge and was influenced by the matte grade and the level of oxygen enrichment.     

L2网络在喷煤中的应用

包钢炼铁厂喷煤系统于1999年12月至2000年5月分别对I、Ⅱ、Ⅲ、Ⅳ系列进行工艺改造,同时增加了西门子计算机,并实现四个系列两套计算机间的联网控制。     

Pallidal afferent territory of the Macaca mulatta thalamus: neuronal and synaptic organization of the VAdc

Ventral anterior thalamic nucleus pars densicellularis (VAdc) as delineated earlier (Ilinsky and Kultas-Ilinsky [1987] J. Comp. Neurol. 262:331-364) was analyzed by using qualitative and quantitative neuroanatomical techniques. Projection neurons (PN), retrogradely labeled with wheat germ agglutinin conjugated horseradish peroxidase from the cortex, were small to medium in size (mean area, 312 microm2) with numerous primary dendrites displaying a tufted branching pattern. Local circuit neurons (LCN), immunoreactive for gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase, were small (mean area, 110 microm2), and gave off few dendrites. Two subpopulations of GABA positive boutons (F1 type) were distinguished: large (mean area, 2.6 microm2) terminals with symmetric synapses containing few pleomorphic vesicles and numerous mitochondria densely covered proximal PN sites; smaller F1 boutons with a slightly different morphology contacted mostly distal PN dendrites. Two subpopulations of terminals containing round vesicles and forming asymmetric synapses were distinguished by bouton size (mean areas, 0.4 microm2 and 1.6 microm2, respectively). These targeted mainly distal PN dendrites, but some synapsed proximally next to large F1 boutons. On distal dendrites, representatives of both types were labeled from the cortex. The density of boutons with symmetric and asymmetric synapses (the number of boutons per 100 microm of PN membrane length) was 3.3:0.2 on primary, 2.5:1.2 on secondary, and 0.8:12 on distal dendrites. The numerical density of synapses formed by presynaptic LCN dendrites on all PN levels was 20 to 40 times less than that of axon terminals at the same sites. Afferent input to LCN from boutons of all types, including that from 50% of labeled cortical boutons, mainly targeted distal dendrites. Overall, the findings suggest that PN in VAdc receive massive inhibitory input proximally intermingled with some presumably excitatory input, and that LCN contribution to PN inhibition is modest.