Contributions of noradrenergic neurones of the locus coeruleus to the temporal damping of linear electrocortical waves

The preceeding paper (Wright et al. 1985a) gives evidence that mesotelencephalic dopaminergic neurones regulate gross electrocortical waves with linear properties, by influencing the strength of their driving signals and temporal damping. The present study further generalises the findings to ascending noradrenergic neurones, which have different fields of termination to dopaminergic fibres. It is shown that: Estimates of the major groups of natural frequencies for the telencephalic system obtained from curve-fitting the ratio changes in the power spectrum attributable to unilateral noradrenergic neurone lesion, are again centered about the frequencies of the major cerebral rhythms. Estimates of electrode transfer characteristics, using parameters obtained from curve fitting ratio changes in power, in conjunction with the raw left and right power spectra, are again found to be equal left and right, as required by the theoretical derivation. Changes in relative amplitude of electrocortical waves and their relative phase are significantly in accord with the relationship expected from theory.     

Amplitude and phase relations of electrocortical waves regulated by transhypothalamic dopaminergic neurones: A test for a linear theory

We have previously proposed that electrocortical activity (EEG) arises as a manifestation of linear waves generated by resonance among telencephalic neurones, and that this activity is controlled in part by ascending neurones from the brain-steim, which regulate the damping of each resonance. The presentexperiments focus on a specific class of ascending neurones, the mesotelencephalic dopaminergic cells, because these cells are thought to mediate important psychological effects, and are conveniently subject to selective lesion. A critical test of the theory is undertaken, by performing selective unilateral lesion, assessing the changes in the power spectrum of the EEG attributable to lesion, and determining whether the changes in phase of the EEG correspond to that predicted from the changes in power. Results support the theory, although the model order applicable in these experiments is inadequate. The consequences of these findings for automata theory, linear network theory and their application to mammalian brains are briefly discussed.     

A test for constant natural frequencies in electrocortical activity under lateral hypothalamic control

An initial test for a theory of lateral hypothalamic regulation of electrocortical activity is undertaken. The theory supposes lateral hypothalamic input directly or indirectly damps telencephalic resonances involving linear wave phenomena, enabling this pathway to act as parametric control of information processing in cortical neural networks. Relative changes in left and right electrocortical power spectra are used to test for the presence of resonant modes with constant natural frequencies in conditions of asymmetrical damping, following unilateral lesion of the lateral hypothalamus. Natural frequency values for the modes clustered about center frequencies in the EEG band are obtained. This method has the advantage of minimising the effects of time-variation and the recorded signal's distortion from the electrocortical local spatial average, but limits consideration to five dominant modes of resonance. The uncertainty of true model order, and errors in curve-fitting impose limitations on the test.     

Inference of a stable dispersion relation for electrocortical activity controlled by the lateral hypothalamus

A second test is undertaken for a theory of linear wave motion in electrocortical waves, under lateral hypothalamic control via regulation of damping. This test invokes a general property of linear systems, namely that wave motion with characteristic natural frequencies implies fixed phase velocities associated with each wavelength, independent of the changes in hypothalamic input. A means of testing the invariance of this dispersion relation at the point of recording is derived from a simplified biophysical model for waves in a dipole layer. The method avoids some problems implicit in direct spatio-temporal wave analysis. Results confirm that the model under test is internally consistent, and is also consistent with other findings concerning the origin and spatial nature of the EEG.     

Effect of thyrotropin-releasing hormone (TRH) on EEG topography

EEG topography by a microcomputer system (ATAC-3700 Nihon-Kohden) was performed in the rabbit in order to investigate the mechanism of TRH action on the brain wave. Power spectral analysis was carried out using a fast Fourier transform algorithm. The square root of the power spectra was defined as the equivalent potential over each frequency band by Ueno & Matsuoka's method. Potential fields of EEG frequency band were printed out on the topographic maps. The potentials of the electrocortical delta and theta waves were high, while the potentials of the alpha, beta 1 and beta 2 waves were low. Stimulation of the nucleus ventralis anterior (VA) by 3 Hz and 8 Hz resulted in a decrease in these potentials, especially, those of the alpha, beta 1 and beta 2 waves. The potentials of the alpha and fast waves were increased following unilateral destruction of VA. In the rabbit, in which TRH 0.5 mg/kg had been administered beforehand, there was no decrease in the potential of each wave induced by stimulation of VA with frequencies of 3 Hz and 8 Hz. The findings suggest involvement of the diffuse thalamocortical projection system in the activation of EEG by TRH.     

Dopaminergic mechanisms in the pathogenesis of schizophrenia.

The dopamine hypothesis of schizophrenia has been the dominant theoretical construction guiding research and treatment of the schizophrenic disorders over the past generation. This hypothesis, in its simplest guise, posits the presence of a functional alteration in central dopaminergic systems in the brains of schizophrenic patients. Recent findings have resulted in a greater understanding of the complexity of the central dopaminergic systems and have led to revisions of the hypothesis of a simple functional hyperactivity of central dopaminergic systems. These recent data suggest that there may be regionally restricted changes in the function of the mesotelencephalic dopamine system, and that these changes may be in opposite directions. Such changes may be associated with dysfunctions of interactions between distinct dopaminergic terminal field regions, and may be subserved by functional derangements in other transmitter systems or reflect regionally restricted changes in expression or function of distinct dopamine receptors or catecholamine synthetic enzymes. A recent FASEB symposium reviewed new advances in molecular biology, biochemistry, pharmacology, anatomy, and systems neuroscience as they relate to schizophrenia, and discussed the implications of these data for guiding future research and treatment strategies.     

Morpho-functional study of the glutamatergic,cholinergic, and dopaminergic systems interaction in the striatum

Interaction among glutamat-, cholin-, and dopaminergic systems in the neostriatum of white rats with unilateral local lesion of the mesostriatal dopaminergic system. Both synaptic and interneuronal non-synaptic interactions among the neurochemical systems under study, were revealed.     

Systemic Administration of NMDA and AMPA Receptor Antagonists Reverses the Neurochemical Changes Induced by Nigrostriatal Denervation in Basal Ganglia

In Parkinson's disease, nigrostriatal denervation leads to an overactivity of the subthalamic nucleus and its target areas, which is responsible of the clinical manifestations of the disease. Because the subthalamic nucleus uses glutamate as neurotransmitter and is innervated by glutamatergic fibers, pharmacological blockade of glutamate transmission might be expected to restore the cascade of neurochemical changes induced by a dopaminergic denervation within the basal ganglia. To test this hypothesis, two types of glutamate antagonists, the NMDA receptor antagonist MK-801 and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist LY293558, were administered systemically, either alone or in combination with L-DOPA, in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine pathway. The effect of treatment was assessed neurochemically by analyzing at the cellular level the functional activity of basal ganglia output structures and the subthalamic nucleus using the expression levels of the mRNAs coding for glutamic acid decarboxylase and cytochrome oxidase, respectively, as molecular markers of neuronal activity. The present study shows that treatment with glutamate antagonists, and particularly with AMPA antagonists, alone or in combination with L-DOPA, reverses the overactivity of the subthalamic nucleus and its target areas induced by nigrostriatal denervation. These results furnish the neurochemical basis for the potential use of glutamate antagonists as therapeutic agents in Parkinson's disease.     

Characterization of specific in vivo binding of neuroleptic drugs in rat brain.

Lesioning of the rat striatum with kainic acid may provide a useful animal model with which to study Huntington's Disease since, in both situations, changes in several neurochemical parameters appear similar. In this study, we examined the time course of dopaminergic (DA) and muscarinic cholinergic (MCHOL) receptor alterations after kainic acid injection into the rat striatum. As early as two days after unilateral, intrastriatal injection of kainic acid, most striatal perikaya in the injected area had been destroyed as seen by histological examination. A progressive decrease in the DA and MCHOL receptors continued which was not due to changes in their affinity for their respective receptors. By 48 days after injection, there was about 75% decrease in DA receptors and about a 65% decrease in MCHOL receptors. The DA receptor loss is similar in extent to the reported loss in activity of striatal, dopamine-stimulated adenylate cyclase after kainic acid lesion. The DA and MCHOLreceptor loss is similar to the reported loss of neostriatal DA and MCHOL receptors in Huntington's Disease.     

Correlation between rotational behaviors and neurochemical changes associated with damage of rat striatum: Analysis using unilateral microinjection of kainic acid

The correlation between rotational behaviors and neurochemical changes associated with the striatal damage induced by an unilateral microinjection of kainic acid were investigated. Shortly after the unilateral striatal injection of kainic acid, rats exhibited contralateral rotational behaviors, and these changes were antagonized by the simultaneous striatal injection of haloperidol. On the other hand, systemic injection of methamphetamine to animals having the lesion on nigro-striatal dopaminergic neurons exhibited ipsilateral turnings. In addition, it was found that the release of [¹⁴C]dopamine from striatal slices was increased by the in vitro addition of kainic acid. Following 2 days after the striatal injection of kainic acid and thereafter, the rats exhibited ipsilateral rotational behaviors and microinjection of muscimol into the ipsilateral substantia nigra of these animals altered turning movements to a contralateral type. Simultaneous nigral injection of bicuculline antagonized to the muscimol-induced contralateral turnings. These results suggest that the increase of dopamine release from dopaminergic neurons in the striatum may be involved in the occurrence of contralateral turning behaviors observed shortly after the striatal kainic acid treatment. The present results also suggest that changes in the functional states of striatonigral GABA-ergic neurons may play an important role in the occurrence of ipsilateral rotational movements at a late stage following the striatal injection of this agent.     

Time Course of Adaptations in Dopamine Biosynthesis, Metabolism, and Release Following Nigrostriatal Lesions: Implications for Behavioral Recovery from Brain Injury

Alterations in neostriatal dopamine metabolism, release, and biosynthesis were determined 3, 5, or 18 days following partial, unilateral destruction of the rat nigrostriatal dopamine projection. Concentrations of dopamine and each of its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 3-methoxytyramine (3-MT) were markedly decreased in the lesioned striata at 3, 5, or 18 days postoperation. The decline in striatal high-affinity [3H]dopamine uptake closely matched the depletion of dopamine at 3 and 18 days postoperation. However, neither DOPAC, HVA, nor 3-MT concentrations were decreased to as great an extent as dopamine at any time following lesions that depleted the dopamine innervation of the striatum by greater than 80%. In these more severely lesioned animals, dopamine metabolism, estimated from the ratio of DOPAC or HVA to dopamine, was increased two- to four-fold in the injured hemisphere compared with the intact hemisphere. Dopamine release, estimated by the ratio of 3-MT to dopamine, was more increased, by five- to sixfold. Importantly, the HVA/dopamine, DOPAC/dopamine, and 3-MT/dopamine ratios did not differ between 3 and 18 days postlesioning. The rate of in vivo dopamine biosynthesis, as estimated by striatal DOPA accumulation following 3,4-dihydroxyphenylalanine (DOPA) decarboxylase inhibition with NSD 1015, was increased by 2.6- to 2.7-fold in the surviving dopamine terminals but again equally at 3 and 18 days postoperation. Thus, maximal increases in dopamine metabolism, release, and biosynthesis occur rapidly within neostriatal terminals that survive a lesion. This mobilization of dopaminergic function could contribute to the recovery from the behavioral deficits of partial denervation by increasing the availability of dopamine to neostriatal dopamine receptors. However, these presynaptic compensations are not sufficient to account for the protracted (at least 3-week) time course of sensorimotor recovery that has been observed following partial nigrostriatal lesion.     

Energy and plastic metabolism of the heart muscle in rabbits undergoing thyroid irradiation with decimeter waves

The functional state of myocardial mitochondria, the glycogen and nucleic acid contents in myocardium, and morphometry of structural elements of cardiomyocytes and myocardial capillary network were investigated in order to select the optimal regimen of decimeter wave exposures with power density of 10, 120 and 240 mW/cm2 on the area of thyroid gland. It was shown that the thyroid gland exposure to decimeter waves at these intensities resulted in functional shifts in energy and plastic processes in myocardium and capillary blood supply. These changes increased to a considerable extent as the intensity of exposure was increasing and reached the maximum at power density of 240 mW/cm2 but event at this intensity there was not found the injurious effect of decimeter waves on the myocardium.     

Spillover of fish naïveté from marine reserves

Spillover of adult fish biomass is an expected benefit from no‐take marine reserves to adjacent fisheries. Here, we show fisher‐naïve behaviour in reef fishes also spills over from marine reserves, potentially increasing access to fishery benefits by making fishes more susceptible to spearguns. The distance at which two targeted families of fishes began to flee a potential fisher [flight initiation distance (FID)] was lower inside reserves than in fished areas, and this reduction extended outside reserve boundaries. Reduced FID persisted further outside reserves than increases in fish biomass. This finding could help increase stakeholder support for marine reserves and improve current models of spillover by informing estimates for spatial changes in catchability. Behavioural changes of fish could help explain differences between underwater visual census and catch data in quantifying the spatial extent of spillover from marine reserves, and should be considered in the management of adjacent fisheries.     

帕金森病大鼠STN-DBS刺激8天后黑质内胶质细胞的形态学变化

目的：观察丘脑底核脑深部电刺激（STN—DBS）慢性刺激后黑质内胶质细胞和多巴胺能细胞的变化。方法：取50只健康Wistar雄性大鼠随机分为假造模组（n=10）和6-羟基多巴胺（6-OHDA）组（11=40）。立体定向单侧造模成功后将6-OHDA组随机分为假手术组（n=10）,假刺激组（n=15）,刺激组（n=15）。刺激组和假刺激组植入STN—DBS,假手术组进行手术但不植入电极。刺激组术后第8d开始每日在固定时间给予连续脉冲刺激,持续时间30mins,连续8d。假刺激组刺激方法同上但关闭电源。在STN—DBS刺激前、刺激时和刺激后观察2mins内大鼠阿扑吗啡旋转次数。刺激结束后将大鼠断头取脑固定,取左侧黑质脱水、透明、浸蜡、包埋、切片,染色。电镜下观察细胞形态并进行细胞计数。结果：帕金森大鼠植入STN—DBS刺激后症状显著改善。慢性刺激8天后刺激组黑质内的星形胶质细胞和多巴胺能细胞均较假刺激组和假手术组明显增加并有统计学意义,而刺激组的小胶质细胞较假刺激组和假手术组有所减少但无统计学意义。结论：STN-DBS慢性刺激可以促使黑质内星形胶质细胞增多,小胶质细胞减少,对黑质内爹巴胺能细胞有一定的保护作用。     

Quantifying Neural Oscillatory Synchronization: A Comparison between Spectral Coherence and Phase-Locking Value Approaches

Synchronization or phase-locking between oscillating neuronal groups is considered to be important for coordination of information among cortical networks. Spectral coherence is a commonly used approach to quantify phase locking between neural signals. We systematically explored the validity of spectral coherence measures for quantifying synchronization among neural oscillators. To that aim, we simulated coupled oscillatory signals that exhibited synchronization dynamics using an abstract phase-oscillator model as well as interacting gamma-generating spiking neural networks. We found that, within a large parameter range, the spectral coherence measure deviated substantially from the expected phase-locking. Moreover, spectral coherence did not converge to the expected value with increasing signal-to-noise ratio. We found that spectral coherence particularly failed when oscillators were in the partially (intermittent) synchronized state, which we expect to be the most likely state for neural synchronization. The failure was due to the fast frequency and amplitude changes induced by synchronization forces. We then investigated whether spectral coherence reflected the information flow among networks measured by transfer entropy (TE) of spike trains. We found that spectral coherence failed to robustly reflect changes in synchrony-mediated information flow between neural networks in many instances. As an alternative approach we explored a phase-locking value (PLV) method based on the reconstruction of the instantaneous phase. As one approach for reconstructing instantaneous phase, we used the Hilbert Transform (HT) preceded by Singular Spectrum Decomposition (SSD) of the signal. PLV estimates have broad applicability as they do not rely on stationarity, and, unlike spectral coherence, they enable more accurate estimations of oscillatory synchronization across a wide range of different synchronization regimes, and better tracking of synchronization-mediated information flow among networks.     

Flow microfluorometric studies of lectin binding to mammalian cells. II. Estimation of the surface density of receptor sites by multiparameter analysis

A flow-system multiparameter cell analyzer that simultaneously measures and processes fluorescence and cell volume signals from single cells was used to study the binding of fluorescein-conjugated Concanavalin A (Con A–F) to the cell surface. Cells reacted with Con A–F were passed through a flow chamber where sensors measured both cell volume and fluorescence of each individual cell. Sensor signals were electronically processed by first converting the cell volume signals to two-thirds power (proportional to surface area) and then forming the fluorescence-to-surface area ratio. These ratios, which were considered as estimates of the surface density of binding sites, were displayed as frequency distribution histograms using a multichannel pulse-height analyzer for various cell populations differing in cell size. Comparisons between cell lines showed characteristic differences in binding site density. Cell cycle dependent changes were not found for CHO cells synchronized by mitotic selection. An important benefit of this analysis method was the ability to quantitate very weak cell surface fluorescence.     

delta 9-Tetrahydrocannabinol elicited ipsilateral circling behavior in rats with unilateral nigral lesion

The present study was designed to examine the influence of delta 9-tetrahydrocannabinol (THC) on the central dopaminergic system using circling behavior. THC 5 mg/kg i.p. produced ipsilateral circling in rats with unilateral nigral lesion by 6-hydroxy-dopamine. THC-induced ipsilateral circling was completely antagonized by 0.2 mg/kg of haloperidol. These findings suggest that THC may cause a presynaptic stimulation of nigrostriatal dopaminergic neurons.     

The effects of raising intracranial pressure on breathing movements, eye movements and electrocortical activity in fetal sheep

Extra-dural or cerebroventricular intracranial pressure was measured in 7 unanaesthetized fetal sheep (123-137 days gestation). Basal intracranial pressure was 6.7 +/- 1.7 mmHg, but there were many transient increases of pressure in association with spontaneous changes of amniotic pressure, fetal intrathoracic pressure, and particularly when the fetal nuchal muscles were active. These spontaneous increases of intracranial pressure were often associated with cessation of breathing movements and change of the electrocorticogram from low to high voltage activity. To test whether increased intracranial pressure influenced breathing movements and electrocortical activity, intracranial pressure was raised either by occluding the superior vena cava for 1 min with an implanted extravascular cuff, or by extra-dural injection of 0.3-1.0 ml of 0.9% NaCl. Increasing the intracranial pressure 5-15 mmHg by either method during low voltage electrocortical activity caused cessation of breathing movements, electro-ocular activity, and change of the electrocorticogram from low to high voltage in a significant proportion of trials. We propose that natural fluctuations of intracranial pressure caused by compression of the fetal body or skull, by body movements or by uterine activity, may cause changes in electrocortical activity and breathing movements.