Nonopiate effects of dynorphin and des-Tyr-dynorphin

Intracerebroventricular administration of dynorphin produced potent and long-lasting effects on motor function and the electroencephalogram in rats. In addition, local iontophoretic or pressure ejection of dynorphin consistently inhibited hippocampal unit activity. None of these effects were significantly affected by naloxone even at high doses. Moreover, a fragment of dynorphin that failed to displace any of a number of tritiated narcotics from rat brain homogenates produced similar effects on these physiological measures in vivo. On the basis of a variety of criteria for "opiate action," the results suggest that a second biologically active site within the dynorphin sequence is capable of quite potent but nonopiate effects.     

一类分流抑制细胞神经网络概周期解的存在性

研究各细胞元拥有各自信号处理函数并具分布时滞的变系数二维分流抑制细胞神经网络的概周期解的存在性,获得了存在性的一个充分条件．     

农产品价格上涨与通胀因果关系的实证研究——基于SUR模型和GIRF 方法的组合研究

由于Granger因果关系检验的局限性，使农产品价格上涨与通胀之间因果关系的传导方向一直存在争议.为此，本文用似无关回归模型（SUR）和广义脉冲响应函数（GIRF）相结合的组合研究模式对农产品价格上涨和通胀之间的因果关系进行了实证研究.首先，利用似无关回归模型构造统计量检验各种传导机制的存在性；其次，在农产品价格上涨与通胀之间双向传导机制都存在的情况下，利用广义脉冲响应函数方法对各种传导机制的显著性进行了对比.结论认为，农产品价格上涨导致通胀的因果关系更显著.     

Psychotomimesis mediated by kappa opiate receptors

The kappa opioid agonists are analgesics that seem to be free of undesired morphine-like effects. Their dysphoric actions observed with the kappa agonist cyclazocine are thought to be mediated by an action at sigma-phencyclidine receptors. The benzomorphan kappa agonist MR 2033 is inactive at sigma-phencyclidine receptors. In male subjects, the opiate-active (-)-isomer, but not the (+)-isomer, elicited dose-dependent dysphoric and psychotomimetic effects that were antagonized by naloxone. Thus, kappa opiate receptors seem to mediate psychotomimetic effects. In view of the euphorigenic properties of mu agonists, our results imply the existence of opposed opioid systems affecting emotional and perceptual experiences.     

神经肽与针刺调整作用的可能关系

当前,对神经肽(neuropeptides)的研究进展十分迅速。应用免疫学方法,神经肽在神经系统中的分布已经能够准确定位,不论中枢或外周神经中均含有肽能神经成份,它已经成为机体正常生理活动的一个新的调节或控制系统。不少学者在论证神经肽的递质作用时,还认为神经肽可以作为神经调制物质(neuromodulator),它能修饰神经元对其它递质的反应。因此,神经肽对机体功能活动的影响是广泛而深刻的。不少针刺穴位所产生的效应与某些神经肽的生理功能十分相似,本文综述有关资料,说明神经肽中的内源性鸦片样物质(OLS),特别是脑啡肽和内啡肽参与针刺镇痛过程。同时,根据现有的有关实验报道和资料,有迹象表明神经肽与针刺对机体的调整作用可能存在着一定的联系。本文就现有资料对其相关性进行了初步分析,提出密切注意神经肽研究的进展,并将神经肽研究和对针刺疗法作用原理的探讨结合起来,以期有助于针刺机理或针刺的部分作用机制的阐明,促进针刺疗法的进一步发展的观点。     

Neural correlates of a magnetic sense

Many animals rely on Earth's magnetic field for spatial orientation and navigation. However, how the brain receives and interprets magnetic field information is unknown. Support for the existence of magnetic receptors in the vertebrate retina, beak, nose, and inner ear has been proposed, and immediate gene expression markers have identified several brain regions activated by magnetic stimulation, but the central neural mechanisms underlying magnetoreception remain unknown. Here we describe neuronal responses in the pigeon's brainstem that show how single cells encode magnetic field direction, intensity, and polarity; qualities that are necessary to derive an internal model representing directional heading and geosurface location. Our findings demonstrate that there is a neural substrate for a vertebrate magnetic sense.     

Neuronal circuits: an evolutionary perspective

To understand neural circuits completely, it is necessary to know not only how they work, but also why they work that way. Answers to the latter question have been almost teleological in their assumption of optimal design. However, close examination of certain systems has revealed features that apparently lack adaptive value. Their existence can be understood only if the evolution of these circuits is considered and, in particular, how nonadaptive determinants have guided that evoluton.     

Opiate analgesia: evidence for mediation by a subpopulation of opiate receptors

Naloxazone, a hydrazone derivative of the opiate antagonist naloxone, has a high affinity for opiate receptor binding sites. Naloxazone injections reduce opiate receptor binding to extensively washed mouse brain membranes for more than 24 hours, suggesting that the effect is irreversible. High-affinity binding sites are abolished by this treatment, whereas low-affinity sites are unaffected. Naloxazone treatment blocks the analgesic effects of morphine for at least 24 hours but does not prevent death from high doses of morphine. Thus analgesic but nonlethal opiate effects may be mediated by the high-affinity subpopulation of opiate receptors.     

An opiate binding site in the rat brain is highly selective for 4,5-epoxymorphinans

In vitro binding studies have demonstrated the existence of multiple opiate receptor types. An additional site in the rat brain (termed the lambda site) is distinct from the established types by its selectivity for 4,5-epoxymorphinans (such as naloxone and morphine). While the lambda site displays a high affinity for naloxone in vivo and in vitro in fresh brain membrane homogenates, these sites rapidly convert in vitro to a state of low affinity. The regional distribution of the lambda site in the brain is strikingly different from that of the classic opiate receptor types.     

Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801.

The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is an important mediator of several forms of neural and behavioral plasticity. The present studies examined whether NMDA receptors might be involved in the development of opiate tolerance and dependence, two examples of behavioral plasticity. The noncompetitive NMDA receptor antagonist MK-801 attenuated the development of tolerance to the analgesic effect of morphine without affecting acute morphine analgesia. In addition, MK-801 attenuated the development of morphine dependence as assessed by naloxone-precipitated withdrawal. These results suggest that NMDA receptors may be important in the development of opiate tolerance and dependence.     

Spinal sympathetic neurons: possible sites of opiate-withdrawal suppression by clonidine

Morphine, methadone, meperidine, fentanyl, and clonidine rapidly depressed transmission through sympathetic preganglionic neurons in cats with the spinal cord transected. Naloxone promptly antagonized this effect of the opiates but not that of clonidine which was reversed by alpha 2-adrenergic receptor antagonists. The independent depression of preganglionic neurons by clonidine may contribute to the ability of this drug to depress the symptoms of opiate withdrawal that are characterized by sympathetic hyperactivity.     

Evidence for the neuropeptide cholecystokinin as an antagonist of opiate analgesia

The endogenous neuropeptide cholecystokinin, when administered systemically or perispinally, potently antagonizes opiate analgesia produced by foot shock and morphine. Nonopiate foot-shock analgesia is not reduced by this neuropeptide. The spinal cord appears to be a critical site of cholecystokinin action. These experiments suggest a physiological role for cholecystokinin as a specific opiate antagonist in analgesia-mediating systems. A similar mode of action may explain other behavioral effects of cholecystokinin, such as suppression of food intake.     

Defensive behaviors in infant rhesus monkeys: environmental cues and neurochemical regulation

To survive, primates must detect danger in time to activate appropriate defensive behaviors. In this study, the defensive behaviors of infant rhesus monkeys exposed to humans were characterized. It was observed that the direction of the human's gaze is a potent cue for the infant. Infants separated from their mothers were active and emitted frequent distress vocalizations. When a human entered the room but did not look at the infant, it became silent and froze in one position. If the human stared at the infant, it responded with aggressive barking. Alterations of the opiate system affected the frequency of the infant's distress calls without affecting barking and freezing, whereas benzodiazepine administration selectively reduced barking and freezing. This suggests that opiate and benzodiazepine systems regulate specific defensive behaviors in primates and that these systems work together to mediate behavioral responses important for survival.     

Neuronal plasticity: increasing the gain in pain

We describe those sensations that are unpleasant, intense, or distressing as painful. Pain is not homogeneous, however, and comprises three categories: physiological, inflammatory, and neuropathic pain. Multiple mechanisms contribute, each of which is subject to or an expression of neural plasticity-the capacity of neurons to change their function, chemical profile, or structure. Here, we develop a conceptual framework for the contribution of plasticity in primary sensory and dorsal horn neurons to the pathogenesis of pain, identifying distinct forms of plasticity, which we term activation, modulation, and modification, that by increasing gain, elicit pain hypersensitivity.     

Intrinsic mechanisms of pain inhibition: activation by stress

Portions of the brain stem seem normally to inhibit pain. In man and laboratory animals these brain areas and pathways from them to spinal sensory circuits can be activated by focal stimulation. Endogenous opioids appear to be implicated although separate nonopioid mechanisms are also evident. Stress seems to be a natural stimulus triggering pain suppression. Properties of electric footshock have been shown to determine the opioid or nonopioid basis of stress-induced analgesia. Two different opioid systems can be activated by different footshock paradigms. This dissection of stress analgesia has begun to integrate divergent findings concerning pain inhibition and also to account for some of the variance that has obscured the reliable measurement of the effects of stress on tumor growth and immune function.     

Prolactin and growth hormone release by morphine in the rat: different receptor mechanisms

Concentrations of prolactin and growth hormone in the serum of rats were significantly increased by morphine. Dose response studies demonstrated that maximum prolactin release required lower doses of morphine than those needed for the maximum growth hormone response. Selective blockade of mu 1 (high affinity) opiate receptor with the irreversible antagonist naloxazone reduced morphine-induced peak concentrations of prolactin by 80 percent while increasing peak growth hormone levels by 250 percent. These results suggest different receptor mechanisms for the opiate modulation of the two hormones. The mu 1 (high affinity) receptor sites appear to mediate the morphine-induced release of prolactin but not growth hormone.     

Opiates and pain pathways: demonstration of enkephalin synapses on dorsal horn projection neurons

The participation of the opiate peptide enkephalin in the neural circuitry of the dorsal horn was examined at the light and ultrastructural level through the use of the combined techniques of immunocytochemistry and retrograde transport of horseradish peroxidase. Enkephalin immunoreactive axonal endings made direct synaptic contact with the soma and proximal dendrites of dorsal horn thalamic projection neurons. This observation demonstrates that one major synaptic site of enkephalin modulation of the transfer of nociceptive information in the dorsla horn is on the projection neurons themselves.U     

Schema-dependent gene activation and memory encoding in neocortex

When new learning occurs against the background of established prior knowledge, relevant new information can be assimilated into a schema and thereby expand the knowledge base. An animal model of this important component of memory consolidation reveals that systems memory consolidation can be very fast. In experiments with rats, we found that the hippocampal-dependent learning of new paired associates is associated with a striking up-regulation of immediate early genes in the prelimbic region of the medial prefrontal cortex, and that pharmacological interventions targeted at that area can prevent both new learning and the recall of remotely and even recently consolidated information. These findings challenge the concept of distinct fast (hippocampal) and slow (cortical) learning systems, and shed new light on the neural mechanisms of memory assimilation into schemas.     

Nucleus accumbens long-term depression and the expression of behavioral sensitization

Drug-dependent neural plasticity related to drug addiction and schizophrenia can be modeled in animals as behavioral sensitization, which is induced by repeated noncontingent or self-administration of many drugs of abuse. Molecular mechanisms that are critical for behavioral sensitization have yet to be specified. Long-term depression (LTD) of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor (AMPAR)-mediated synaptic transmission in the brain has been proposed as a cellular substrate for learning and memory. The expression of LTD in the nucleus accumbens (NAc) required clathrin-dependent endocytosis of postsynaptic AMPARs. NAc LTD was blocked by a dynamin-derived peptide that inhibited clathrin-mediated endocytosis or by a GluR2-derived peptide that blocked regulated AMPAR endocytosis. Systemic or intra-NAc infusion of the membrane-permeable GluR2 peptide prevented the expression of amphetamine-induced behavioral sensitization in the rat.     

基于神经元晶体管和忆阻器的 Hopfield 神经网络及其在联想记忆中的应用

随着人工智能的高速发展,越来越多的神经元模型相继被提出,现有的神经元电路主要由普通晶体管、运算放大器等高功耗器件构成,存在结构复杂、集成度不高、兼容性差、功耗高、阈值调节难度高的缺点.针对以上不足,首次提出了一种全新的神经元结构,该结构仅由神经元晶体管、忆阻器和普通电阻构成,相比传统神经元电路,不包含复杂的差分运算电路以及电流与电压信号的转换电路,电路结构简单,同时具有良好的电路兼容性,可用于大规模集成.该结构利用神经元晶体管的加权求和特性以及阈值可控功能来模拟神经元信息传导过程,同时利用阈值忆阻器的阈值特性和阻值连续变化能力来设定和更新突触权值,使得该新型神经元结构不仅能实现传统神经元电路功能的同时,还具有能耗低、阈值动态可控、权值可编程的优点,不仅极大地简化了网络结构,还能加强网络性能.其次,还提出了基于这种新型神经元结构的忆阻离散Hopfield神经网络,该忆阻神经网络有助于促进人工神经形态系统的硬件实现,使神经网络系统能耗降低,集成度极大地提高,将这种网络运用在联想记忆和彩色数字图像恢复中,进一步说明了基于全新神经元结构的忆阻离散hopfield神经网络的实用性以及有效性.