The role of spatio-temporal firing patterns in neuronal development of sensory systems

The emergence of precise and orderly sets of neuronal connections often depends upon coordinated electrical activity during the early stages of development. In recent years, an increasing number of reports have shown that neurons of immature sensory systems can spontaneously generate electrical activity that occurs synchronously amongst adjacent cells. These patterns of correlated activity seem to be well suited to the role of providing the cues that are necessary for the activity-dependent refinement of the neural connections in the developing visual, auditory and somatosensory pathways.     

In vivo tracing of pathways and spatio-temporal activity patterns in rat visual cortex using voltage sensitive dyes

We monitored optical signals from cortex stained with a voltage sensitive dye to study activity evoked by intracortical electrical stimulation. The objectives were to study the spatial and temporal spread of activity from intrinsic connections near the stimulating electrode and to develop a new technique to study extrinsic projections from striate cortex to extrastriate target areas. Various measures were made of the time course of the optical signal (latency, rise time, decay time, temporal summation, facilitation versus depression, and presence or absence of a slow undershoot); in general, these measures were found to vary significantly across different response positions, different experiments, and even different runs within the same experiment. The spatial distribution of responses near the stimulating electrode in striate cortex was usually elliptical and was most often elongated along the anterior-posterior axis, with a typical size (full width at 75% max) of 1.3 mm (anterior-posterior axis) by 0.75 mm (medio-lateral axis). In some cases, complex spatio-temporal patterns were observed, in which the position of the maximum optical signal shifted with time or split into multiple peaks. In eight experiments, a response focus was found in extrastriate cortex at an expected location within the lateromedial area (LM). The response focus in LM was typically about half the size of that in striate cortex. In some experiments we observed additional focal responses in the anterolateral visual area (AL). The extrastriate responses showed a significant delay (3-10 ms) in onset and time to peak relative to the striate response. The validity of this technique for determining extrinsic projections was tested in two types of experiments. In the first, stimulation from two electrodes in striate cortex generated response foci consistent with the known topographic organization of area LM. In the second, the optically measured response focus was shown to correlate with the histologically reconstructed projection of a chemical tracer injected near the site of stimulation. We discuss the chain of neurophysiological events that occur during and after focal electrical stimulation and how they relate to the observed optical signal. We conclude that direct passive responses were a small component of our signal, that the component due to action potentials in directly stimulated neurons should have occurred in the first 1-2 ms post stimulus and is small compared to the peak signal, and that overall our signals were probably dominated by a combination of asynchronously occurring action potentials and excitatory and inhibitory synaptic potentials.(ABSTRACT TRUNCATED AT 400 WORDS)     

Developmental trends in auditory-visual cross-modal matching of spatio-temporal patterns.

Compared 10 Ss, boys and girls aged 5, 8, and 11 yrs, in within- and cross-modal matching of auditory and visual spatio-temporal patterns. Separate analyses of hit and false alarm rates showed no effects that could be attributed to a differential development of within- and cross-modal tasks. Contrary to the findings of H. G. Birch and L. Belmont, therefore, the present study provides evidence against the notion that intersensory integration increases with age. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial electrical patterns in simulated neuronal dendrites

Steady state longitudinal distributions of (a) the density of channels conducting an inward transmembrane current of cations, (b) the submembrane concentrations of these cations, and (c) the resting membrane potential, were investigated in a phenomenological model of a cylinder-shaped dendritic process of the neuron. It was found that spatially non-uniform patterns of these distributions occur only if one of the following conditions held (i) an increase in the intracellular concentration of cations conducting an inward passive transmembrane current amplified the active efflux of those cations by the pump and attenuated their passive influx through the voltage dependent channels, with amplification of the efflux lower than attenuation of the influx; (ii) molecules of mobile channels bore a negative electrophoretic charge exposed to the intracellular space and were subject to lateral electrodiffusion in the membrane; (iii) the cations induced a further release of cations from intracellular stores. Numerical simulation studies of the membrane with Na and K channels and Na/K pumps with conditions (i) and (ii) have demonstrated the possibility of the creation of inhomogeneous patterns in the neurites. These inhomogeneous patterns are dissipative structures (DSs), and they can be spatially periodic.     

Mnemonic neuronal activity in somatosensory cortex

Single-unit activity was recorded from the hand areas of the somatosensory cortex of monkeys trained to perform a haptic delayed matching to sample task with objects of identical dimensions but different surface features. During the memory retention period of the task (delay), many units showed sustained firing frequency change, either excitation or inhibition. In some cases, firing during that period was significantly higher after one sample object than after another. These observations indicate the participation of somatosensory neurons not only in the perception but in the short-term memory of tactile stimuli. Neurons most directly implicated in tactile memory are (i) those with object-selective delay activity, (ii) those with nondifferential delay activity but without activity related to preparation for movement, and (iii) those with delay activity in the haptic-haptic delayed matching task but no such activity in a control visuo-haptic delayed matching task. The results indicate that cells in early stages of cortical somatosensory processing participate in haptic short-term memory.     

MFT in complex partial epilepsy: spatio-temporal estimates of interictal activity

Following exposure of CHO-K1 cells to 137Cs irradiation at doses up to 20Gy, a delay in G2 was observed to occur in cells permitted to divide normally, while cells induced to become giants by means of cytochalasin B demonstrated a minimal delay in the transition 2C-8C suggesting that the inhibition of cytokinesis results in modification of one or more cell cycle checkpoints. We postulate that this may occur as a consequence of damage tolerance, or by a feedback loop resulting from the reorganisation of the cytoskeleton that precludes cytokinesis.     

Identification of patterns of neuronal connectivity--partial spectra, partial coherence, and neuronal interactions

We have located a possible chloroquine resistance locus in the genome of the rodent malaria parasite Plasmodium chabaudi. Two genetically distinct clones of the parasite were grown in vivo and allowed to undergo genetic crossing. The clones differed from each other in their susceptibility to chloroquine; AS(3CQ) had been selected for a low level of resistance to the drug whereas AJ is chloroquine-sensitive. Independent recombinant progeny (20) were cloned from the products of two crosses, phenotyped for their susceptibility to chloroquine, and genotyped for their inheritance of 46 chromosome-specific markers. No association was found between chloroquine susceptibility and the inheritance of pcmdr1, the P. chabaudi homologue of the pfmdr1 multi-drug resistance gene of P. falciparum. Also, there was no association between chloroquine susceptibility and the inheritance of a marker linked to a putative chloroquine resistance locus in a P. falciparum cross. However, 16 of the progeny clones showed co-segregation of four linked markers on chromosome 11 with their resistance phenotype. This result suggests that a locus for chloroquine resistance exists on this chromosome in P. chabaudi.     

Clinical patterns of neuronal migrational disorders and parental consanguinity

The primary metabolite of morphine, morphine-6-beta-glucuronide (M-6-G), is reported to contribute to the effects of morphine. The authors investigated the effects of M-6-G on the central nervous system (CNS) after short-term intravenous (i.v.) administration by employing both electroencephalograph (EEG) power spectra analyses and clinical signs as indicators of opioid effects. Three dosages of M-6-G, one dosage of morphine (bolus 10 mg/70 kg and 3.5 mg/70 kg/hour for 4 hours), a combination of morphine and M-6-G, and placebo were administered to 20 healthy volunteers as i.v. bolus plus i.v. infusion for 4 hours. M-6-G was dosed to produce steady state plasma concentrations that were either identical, 2 times, or 3 times higher than the M-6-G plasma concentrations observed after administration of morphine. The EEG background activity and clinical effects were recorded 3.5 hours after the infusion started. M-6-G failed to produce effects on any of the investigated EEG or clinical parameters at the doses tested. In contrast, morphine produced a significant increase in the alpha 1 and delta power of the EEG. In addition, morphine increased the subjects' ratings of tiredness, sickness, vertigo, and drowsiness, and decreased their level of performance in a tracking task. It was concluded that after short-term i.v. administration, M-6-G does not affect the CNS at the doses tested. Therefore, its contribution to clinical effects of morphine after short-term administration is questionable. The missing CNS effects were probably caused by the slow brain permeability of M-6-G, which in short-term treatment might not attain effective CNS concentrations.     

Modulation of neuronal activity by target uncertainty

Visual scenes are composed of many elements and although we can appreciate a scene as a whole, we can only move our eyes to one element of the scene at a time. As visual scenes become more complex, the number of potential targets in the scene increases, and the uncertainty that any particular one will be selected for an eye movement also increases. How motor systems accommodate this target uncertainty remains unknown. The activities of neurons in both the cerebral cortex and superior colliculus are modulated by this selection process. We reasoned that activity associated with target uncertainty should be evident in the saccadic motor system at the final stages of neural processing, in the superior colliculus. By systematically changing the number of stimuli from which a selection must be made and recording from superior colliculus neurons, we found that as the target uncertainty increased, the neural activity preceding target selection decreased. These results indicate that neurons within the final common pathway for movement generation are active well in advance of the selection of a particular movement. This early activity varies with the probability that a particular movement will be selected.     

闽台入境旅游时空发展格局比较分析

闽台入境旅游发展存在明显的时空差异.虽然福建省的土地面积和人口数均大于台湾地区,但历年接待的入境旅游人数却明显少于台湾,只是差距正在不断缩小.目前,闽台国际入境旅游客源国分别以美国和日本居首位.虽然历年入境旅游收入福建省远低于台湾地区,但其占CDP的比重二者渐趋一致.闽台入境旅游发展的时空差异是多因素综合作用的结果.其中,台湾入境旅游发展较早,在市场竞争中占据先机具有重要影响;两地旅游发展政策和经济发展轨迹不同等方面也有一定的影响.     

Spontaneous activity: functions of calcium transients in neuronal differentiation

Calcium ions play critical roles in neuronal development. Many excitable cells promote calcium influx across their surface membrane during early stages of differentiation, which can trigger further elevation of intracellular calcium by release from stores. Several distinct types of spontaneous elevations of intracellular calcium occur during development of amphibian spinal neurons, both in culture and in the intact spinal cord. Rapid spikes and slow waves originate by different mechanisms and have separate functions. Spikes are required for neurotransmitter expression and channel modulation. Waves occurring in growth cones appear to regulate neurite extension.     

Modulation of neuronal activity by glial cells in the retina

Glial-neuronal communication was studied by monitoring the effect of intercellular glial Ca2+ waves on the electrical activity of neighboring neurons in the eyecup preparation of the rat. Calcium waves in astrocytes and Müller cells were initiated with a mechanical stimulus applied to the retinal surface. Changes in the light-evoked spike activity of neurons within the ganglion cell layer occurred when, and only when, these Ca2+ waves reached the neurons. Inhibition of activity was observed in 25 of 53 neurons (mean decrease in spike frequency, 28 +/- 2%). Excitation occurred in another five neurons (mean increase, 27 +/- 5%). Larger amplitude Ca2+ waves were associated with greater modulation of neuronal activity. Thapsigargin, which reduced the amplitude of the glial Ca2+ increases, also reduced the magnitude of neuronal modulation. Bicuculline and strychnine, inhibitory neurotransmitter antagonists, as well as 6-Nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX) and D(-)-2-amino-7-phosphonoheptanoic acid (D-AP7), glutamate antagonists, reduced the inhibition of neuronal activity associated with glial Ca2+ waves, suggesting that inhibition is mediated by inhibitory interneurons stimulated by glutamate release from glial cells. The results suggest that glial cells are capable of modulating the electrical activity of neurons within the retina and thus, may directly participate in information processing in the CNS.     

Induction of astroglial gene expression by experimental seizures in the rat: spatio-temporal patterns of the early stages

The levels of glial fibrillary acidic protein mRNA were analysed by in situ hybridization during the first 6 h in experimental models of status epilepticus in the rat. Two different models of status epilepticus were studied: one is produced by the administration of pilocarpine to lithium-treated rats and the other by the intracerebroventricular administration of kainate. Results obtained in the present study showed a very rapid (as early as 1.5 h in periventricular zones of hypothalamus, cerebral cortex, and hippocampal area) up-regulation of GFAP mRNA levels following the pharmacological induction of seizures. Several other areas showed a GFAP activation starting at 3 h such as septum, habenular nuclei, corpus callosum, and cingulum. The comparison of the results obtained in the two models of status epilepticus revealed interesting differences in some brain areas, such as cerebellum and striatum, which can be related to the specific neurotransmitter receptors and neurochemical pathways stimulated by the drugs. Interestingly, some brain areas whose neurons are strongly activated by pilocarpine and kainate (amygdala and CA3 hippocampal field) and that undergo neuronal degeneration did not show the early GFAP response. An interesting spatial feature was observed in several brain regions examined (striatum, septum, and hypothalamus): the response first appeared in the periventricular zones and then diffused to the rest of the brain area. In general GFAP responses in the periventricular zones were early and intense.     

Reentrainment of motor activity and spontaneous neuronal activity in the suprachiasmatic nucleus of Djungarian hamsters

Neurons in the suprachiasmatic nucleus (SCN) of the hypothalamus exhibit a daily rhythm in spontaneous electrical activity. Essentially two methods have been employed to record this circadian rhythm: (1) an in vitro brain slice technique and (2) in vivo multiunit recordings. Reentrainment of a circadian output to a shifted light:dark cycle commonly takes several cycles (depending on the amount of shift) until completed. Such a resetting kinetic has also been shown to be valid for SCN electrical activity if recorded in vivo. In an in vitro slice preparation, however, pharmacologically induced resetting is much faster and lacks transients; that is, a shift is completed within one cycle. This study was designed to probe for the presence of transients in the neuronal activity of the SCN in a brain slice preparation. The authors exposed Djungarian hamsters to an 8-h advanced or delayed light:dark cycle and monitored wheel-running activity during reentrainment. Additional groups of identically treated hamsters were used to record the pattern of spontaneous neuronal activity within the SCN using the brain slice preparation. Neuronal activity exhibited the usual rhythm with high firing rates during the projected day and low firing rates during the projected night. However, following 1 day of exposure to the 8-h advanced light:dark cycle, this rhythm disappeared in 6 of 7 slices. Rhythmicity was still absent following 3 days of exposure to the advanced light:dark cycle (n = 4). By contrast, 3 of 7 slices prepared from hamsters exposed to a delayed light:dark cycle for 3 days exhibited a daily rhythm in electrical activity. Although pharmacological agents reset the in vitro SCN neuronal activity almost instantaneously and in in vivo studies a stable phase relationship to a shifted light:dark cycle occurs gradually over several cycles, the authors did not detect either of these patterns. Such differences in resetting kinetics (e.g., rapid resetting, gradual reentrainment, temporary lack of measurable rhythmicity) may be due to (a) application of a resetting stimulus in vivo versus in vitro, (b) duration of the resetting stimulus, (c) the nature of the resetting stimulus, or (d) the recording technique employed.     

Dorsal spinocerebellar tract neuronal activity in the intact chronic cat

The ability to electrophysiologically identify the axonal projections of lumbar neurons recorded in chronic unanesthetized intact awake animals is a formidable but essential requirement toward understanding ascending sensory transmission under naturally occurring conditions. Chronic immobilization procedures previously introduced by Morales et al. (1981) for intracellular studies of motoneurons are modified and then integrated with procedures for antidromic cellular identification and extracellular recording of upper (or lower) dorsal lumbar spinocerebellar tract (DSCT) neuronal activity, in conjunction with behavioral state recording and drug microiontophoresis. These implant procedures provide up to 6 months of stable recording conditions and, when combined with other techniques, allow individual DSCT neurons to be monitored over multiple cycles of sleep and wakefulness, following the induction into and recovery from barbiturate anesthesia and/or during the juxtacellular microiontophoretic ejection of inhibitory or excitatory amino acid neurotransmitters. The combination of such techniques allows a comprehensive examination of synaptic transmission through the DSCT and other lumbar sensory pathways in the intact normally respiring cat and its modulation during the general anesthetic state. These techniques permit investigations of the supraspinal controls impinging on lumbar sensory tract neurons during wakefulness and other behavioral states such as active sleep.     

Nitric oxide induction of neuronal endonuclease activity in programmed cell death

Neuronal survival is intricately linked to the maintenance of intact DNA. In contrast, neuronal degeneration following nitric oxide (NO) exposure is dependent, in part, on the degradation of DNA through programmed cell death (PCD). We therefore investigated in primary rat hippocampal neurons the role of endogenous deoxyribonucleases, enzymes responsible for metabolically derived DNA cleavage, during NO-induced neurodegeneration. Twenty-four hours following exposure to the NO generators sodium nitroprusside (300 microM) and SIN-1 (300 microM), neuronal survival was reduced from approximately 88 to 23%. Treatment with aurintricarboxylic acid (1-100 microM), an endonuclease inhibitor, during NO exposure increased neuronal survival from 23 to 80% and decreased DNA fragmentation from 70 to 30% over a 24-h period. Enhancement of endonuclease activity alone with zinc chelation actively decreased neuronal survival from approximately 80% to approximately 34%. DNA digestion assays identified not only two constitutively active endonucleases, an acidic endonuclease (pH 4.0-7.0) and a calcium/magnesium-dependent endonuclease (pH 7.2-8.0), but also a NO-inducible magnesium-dependent endonuclease (pH 8.0). In the absence of endonuclease activity, DNA degradation did not occur during NO application, suggesting that endonuclease activity was a requisite pathway for NO-induced PCD. In addition, NO independently altered intracellular pH in ranges that were physiologically relevant for the activity of the endonucleases responsible for DNA degradation. Our identification and characterization of specific neuronal endonucleases suggest that the constitutive endonucleases may play a role in the initial stages of NO-induced PCD, but the subsequent "downstream" degradation of DNA may ultimately be dependent upon the NO-inducible endonuclease.     

Modifications of reward expectation-related neuronal activity during learning in primate striatum

This study investigated neuronal activity in the anterior striatum while monkeys repeatedly learned to associate new instruction stimuli with known behavioral reactions and reinforcers. In a delayed go-nogo task with several trial types, an initial picture instructed the animal to execute or withhold a reaching movement and to expect a liquid reward or not. During learning, new instruction pictures were presented, and animals guessed and performed one of the trial types according to a trial-and-error strategy. Learning of a large number of pictures resulted in a learning set in which learning took place in a few trials and correct performance exceeded 80% in the first 60-90 trials. About 200 task-related striatal neurons studied in both familiar and learning conditions showed three forms of changes during learning. Activations related to the preparation and execution of behavioral reactions and the expectation of reward were maintained in many neurons but occurred in inappropriate trial types when behavioral errors were made. The activations became appropriate for individual trial types when the animals' behavior adapted to the new task contingencies. In particular, reward expectation-related activations occurred initially in both rewarded and unrewarded movement trials and became subsequently restricted to rewarded trials. These changes occurred in parallel with the visible adaptation of reward expectations by the animals. The second learning change consisted in decreases of task-related activations that were either restricted to the initial trials of new learning problems or persisted during the subsequent consolidation phase. They probably reflected reductions in the expectation and preparation of upcoming task events, including reward. The third learning change consisted in transient or sustained increases of activations. These might reflect the increased attention accompanying learning and serve to induce synaptic changes underlying the behavioral adaptations. Both decreases and increases often induced changes in the trial selective occurrence of activations. In conclusion, neurons in anterior striatum showed changes related to adaptations or reductions of expectations in new task situations and displayed activations that might serve to induce structural changes during learning.     

Frequency-dependent inhibition of neuronal activity by topiramate in rat hippocampal slices

1. Topiramate is a structurally novel anticonvulsant which was recently approved for adjunctive therapy in partial and secondarily generalized seizures. The present study was aimed at elucidating the mechanisms underlying the anticonvulsant efficacy of topiramate using intra- and extracellular recording techniques in the in vitro hippocampal slices. 2. When stimuli were delivered every 20 s, topiramate had no measurable effect on both field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs). However, increasing the stimulation frequency from 0.05-0.2 Hz, topiramate significantly decreased the slope of fEPSP and the amplitude of PS in a concentration-dependent manner. The amplitude of presynaptic fiber volley was also reduced. 3. Topiramate did not affect the magnitude of paired-pulse inhibition and monosynaptically evoked inhibitory postsynaptic potentials (IPSPs). 4. Sustained repetitive firing was elicited by injection of long duration (500 ms) depolarizing current pulses (500-800 pA). Superfusion with topiramate significantly reduced the number of action potentials evoked by a given current pulse. 5. After blockade of GABA receptors by bicuculline, burst firing which consisted of a train of several spikes riding on a large depolarizing wave termed paroxysmal depolarizing shift (PDS) was recorded. Application of topiramate reduced the duration of PDS and later spikes with less effect on the initial action potential. 6. These results suggest that frequency-dependent inhibition of neuronal activity due to blockade of Na+ channels may account largely for the anticonvulsant efficacy of topiramate.     

Influence of reward expectation on behavior-related neuronal activity in primate striatum

Rewards constitute important goals for voluntary behavior. This study aimed to investigate how expected rewards influence behavior-related neuronal activity in the anterior striatum. In a delayed go-nogo task, monkeys executed or withheld a reaching movement and obtained liquid or sound as reinforcement. An initial instruction picture indicated the behavioral reaction to be performed and the reinforcer to be obtained after a subsequent trigger stimulus. Movements varied according to the reinforcers predicted by the instructions, suggesting that animals differentially expected the two outcomes. About 250 of nearly 1,500 neurons in anterior parts of caudate nucleus, putamen, and ventral striatum showed typical task-related activations that reflected the expectation of instructions and trigger, and the preparation, initiation, and execution of behavioral reactions. Strikingly, most task-related activations occurred only when liquid reward was delivered at trial end, rather than the reinforcing sound. Activations close to the time of reward showed similar preferences for liquid reward over the reinforcing sound, suggesting a relationship to the expectation or detection of the motivational outcome of the trial rather than to a "correct" or "end-of-trial" signal. By contrast, relatively few activations in the present task occurred irrespective of the type of reinforcement. In conclusion, many of the behavior-related neurons investigated in the anterior striatum were influenced by an upcoming primary liquid reward and did not appear to code behavioral acts in a motivationally neutral manner. Rather, these neurons incorporated information about the expected outcome into their behavior-related activity. The activations influenced by reward several seconds before its occurrence may constitute a neuronal basis for the retrograde effects of rewards on behavioral reactions.