逃逸速率对分子马达定向运动的影响

在考虑逃逸速率的情况下采用主方程方法研究分子马达,计算了逃逸速率对分子马达的漂移速率、扩散系数、停留时间以及分子马达在轨道上移动的距离．通过计算发现,逃逸速率影响分子马达的定向运动．     

Rich Club Organization of Macaque Cerebral Cortex and Its Role in Network Communication

Graph-theoretical analysis of brain connectivity data has revealed significant features of brain network organization across a range of species. Consistently, large-scale anatomical networks exhibit highly nonrandom attributes including an efficient small world modular architecture, with distinct network communities that are interlinked by hub regions. The functional importance of hubs motivates a closer examination of their mutual interconnections, specifically to examine the hypothesis that hub regions are more densely linked than expected based on their degree alone, i.e. forming a central rich club. Extending recent findings of rich club topology in the cat and human brain, this report presents evidence for the existence of rich club organization in the cerebral cortex of a non-human primate, the macaque monkey, based on a connectivity data set representing a collation of numerous tract tracing studies. Rich club regions comprise portions of prefrontal, parietal, temporal and insular cortex and are widely distributed across network communities. An analysis of network motifs reveals that rich club regions tend to form star-like configurations, indicative of their central embedding within sets of nodes. In addition, rich club nodes and edges participate in a large number of short paths across the network, and thus contribute disproportionately to global communication. As rich club regions tend to attract and disperse communication paths, many of the paths follow a characteristic pattern of first increasing and then decreasing node degree. Finally, the existence of non-reciprocal projections imposes a net directional flow of paths into and out of the rich club, with some regions preferentially attracting and others dispersing signals. Overall, the demonstration of rich club organization in a non-human primate contributes to our understanding of the network principles underlying neural connectivity in the mammalian brain, and further supports the hypothesis that rich club regions and connections have a central role in global brain communication.     

The Role of Behavioral Research in the Conservation of Chimpanzees and Gorillas

Chimpanzees and gorillas are among man's closest living relatives, sharing most of the human genetic code and having many similarities to humans in anatomy, physiology, and behavior. Like humans, these apes make and use tools and have strong family bonds. Chimpanzees even show population-specific behaviors similar to those of human cultures. However, chimpanzee and gorilla populations are in dramatic decline due to bushmeat hunting, habitat loss, and the varied risks of small, isolated populations. The first step in conserving the world's ape populations in the wild is to recognize and understand the complexities of these threats. Mitigating the risks takes a deeper understanding of ape behavior. This article provides examples of how gorilla and chimpanzee behavioral studies intersect with, and are critical to, conservation efforts.     

Discriminative behavior and Pavlovian conditioning in the mollusc Pleurobranchaea

The buccal motor system in the sea slug Pleurobranchaea californica is multifunctional; similar sets of neurons and muscles generate different behaviors through similar electrophysiological motor patterns. Such multifunctional systems compromise the traditional practice of identifying a motor pattern and then using that pattern to indicate the behavior in reduced preparations. We address this issue in a series of experiments leading to the comparison of differential Pavlovian conditioning in whole animals with the conditioned behavior of the same animals during electrophysiological recording. Because differential conditioning requires two conditioned stimuli (CSs), we show here that each of two CSs activated the conditioned response from animals after they received the stimulus (CS+) paired with an unconditioned stimulus (UCS). Conditioning sessions consisted of 5 training trials with a 2-h intertrial interval. In one study, experimental animals received a 60-s CS+, derived from beer (Sbr), paired with a 50-s electrical shock UCS whose onset occurred 10 s after the CS+ onset; control animals received the Sbr and UCS explicitly unpaired. In a second study, animals received similar procedures as in the first but with a CS+ consisting of squid homogenate (Ssq). Tests with both CSs showed that animals did not discriminate between Sbr and Ssq before beginning conditioning, but did so afterward. Experimental animals exhibited robust food aversion (withdrawal and suppressed feeding) to the CS+, but retained strong appetitive responses to the CS they did not receive in training; response thresholds to the CS+ changed as much as 1000-fold by comparison to the preconditioning values. Control animals exhibited similar though significantly smaller behavioral changes as the experimental animals. Both stimuli evoked associatively learned responses, but Sbr produced greater experimental-control differences than Ssq did. Two accompanying papers show the results of using both CSs in differential conditioning, and describe the behavioral/electrophysiological comparisons.     

Role of Mental Retardation-Associated Dystrophin-Gene Product Dp71 in Excitatory Synapse Organization,Synaptic Plasticity and Behavioral Functions

Background

Duchenne muscular dystrophy (DMD) is caused by deficient expression of the cytoskeletal protein, dystrophin. One third of DMD patients also have mental retardation (MR), likely due to mutations preventing expression of dystrophin and other brain products of the DMD gene expressed from distinct internal promoters. Loss of Dp71, the major DMD-gene product in brain, is thought to contribute to the severity of MR; however, the specific function of Dp71 is poorly understood.

Methodology/Principal Findings

Complementary approaches were used to explore the role of Dp71 in neuronal function and identify mechanisms by which Dp71 loss may impair neuronal and cognitive functions. Besides the normal expression of Dp71 in a subpopulation of astrocytes, we found that a pool of Dp71 colocalizes with synaptic proteins in cultured neurons and is expressed in synaptic subcellular fractions in adult brains. We report that Dp71-associated protein complexes interact with specialized modular scaffolds of proteins that cluster glutamate receptors and organize signaling in postsynaptic densities. We then undertook the first functional examination of the brain and cognitive alterations in the Dp71-null mice. We found that these mice display abnormal synapse organization and maturation in vitro, altered synapse density in the adult brain, enhanced glutamatergic transmission and reduced synaptic plasticity in CA1 hippocampus. Dp71-null mice show selective behavioral disturbances characterized by reduced exploratory and novelty-seeking behavior, mild retention deficits in inhibitory avoidance, and impairments in spatial learning and memory.

Conclusions/Significance

Results suggest that Dp71 expression in neurons play a regulatory role in glutamatergic synapse organization and function, which provides a new mechanism by which inactivation of Dp71 in association with that of other DMD-gene products may lead to increased severity of MR.     

The Contributions of Motor Neuronal and Muscle Modulation to Behavioral Flexibility in the Stomatogastric System

The stomatogastric nervous system of crustaceans, which controlsthe four parts ofthe foregut, is subject to modulation at alllevels, sensory, central and motor. Modulation of the centralpattern generators, which are themselves made up largely ofmotor neurons, providesfor increased behavioral flexibilityin a variety of ways. First, each of the pattern generatorscan be reconfigured to give multiple outputs. Second, the "boundaries"of the different pattern generators are in fact somewhat fluid,so that the neuronal composition of the pattern generators canbe altered. For example, neurons can switch from one patterngenerator toanother, or two or more pattern generators can fuseto generate an entirely new pattern and thereby produce a newbehavior. The mechanisms responsible for many of these modulationsinclude alterations of both intrinsic properties and synapticinteractions between neurons. In addition, the alteration ofmembrane properties contributes more directly to the behavioraloutput by changing action potential frequency. Finally, themuscles of the stomatogastric system can themselves be modulated,with the cpvl muscle, for example, becoming an endogenous oscillatorin the presence of either dopamine or the peptide FMRFamide.     

The Role of the Organization Structure in the Diffusion of Innovations

Diffusion and adoption of innovations is a topic of increasing interest in economics, market research, and sociology. In this paper we investigate, through an agent based model, the dynamics of adoption of innovative proposals in different kinds of structures. We show that community structure plays an important role on the innovation diffusion, so that proposals are more likely to be accepted in homogeneous organizations. In addition, we show that the learning process of innovative technologies enhances their diffusion, thus resulting in an important ingredient when heterogeneous networks are considered. We also show that social pressure blocks the adoption process whatever the structure of the organization. These results may help to understand how different factors influence the diffusion and acceptance of innovative proposals in different communities and organizations.     

Mechanisms of Virtual Reality Exposure Therapy: The Role of the Behavioral Activation and Behavioral Inhibition Systems

J. A. Gray’s (1975) theory distinguishes between two motivational systems, which he refers to as the behavioral activation system (BAS) and the behavioral inhibition system (BIS). D. C. Fowles (1980) has shown that heart rate responses reflect activity of the BAS, and electrodermal responses reflect activity of the BIS. Both BAS and BIS are reliably activated during in-vivo exposure to fearful situations (F. H. Wilhelm & W. T. Roth, 1998). However, due to the constraints imposed by virtual reality (VR), we hypothesized that VR exposure to fearful situations would activate the BIS alone. To test this hypothesis, a VR free-standing elevator simulation was presented to participants selected for high and low fear of heights. As predicted, the high-anxious group strongly responded electrodermally (effect size d = 1.53), but showed only minimal HR elevations during exposure (d = 0.12), and little other cardiovascular or respiratory changes. The low-anxious control group showed little electrodermal and HR reactivity (d = 0.28 and 0.12). A comparison with data from a previous study demonstrated that this pattern was in stark contrast to the large electrodermal and cardiovascular response observed during situational in-vivo exposure outside the laboratory. We conclude that the BIS, but not BAS, is selectively activated during VR exposure, causing discordance between self-report and commonly used physiological measures of anxiety. Results are discussed within the framework of E. B. Foa & M. J. Kozak’s (1986) emotional processing theory of fear modification, suggesting different mechanisms underlying VR and in-vivo exposure treatments.     

Positive Affect and Cognitive Restoration: Investigating the Role of Valence and Arousal

Positive moods are thought to restore self-control resources following depletion. However, it is not well understood whether this effect is due to affective valence (pleasantness), arousal (activation), or a combination of both. Across four studies, we set out to investigate the role of positive moods on cognitive and behavioral measures of self-regulation in an ego-depletion paradigm. In studies 1 and 2, we independently manipulated affective valence and arousal and assessed self-regulation with a Stroop task. Results did not suggest a restorative effect of either on cognitive resources. In study 3, we employed both behavioral (the ‘handgrip task’) and cognitive (Stroop) assessments of self-regulation. Again, no significant effect of mood was observed on the Stroop task. Additionally, participants did not persist significantly longer on the handgrip task following a positive mood induction. Finally, in study 4, high vs. low states of arousal were manipulated and self-regulation was assessed via pre- and post-manipulation Stroop performance. In study 4, Stroop performance improved slightly more across time points for those in the high arousal condition than for those in the low arousal condition. Therefore, across four studies, we failed to find a consistent pattern of results suggesting that positive moods restore cognitive resources.     

Role of BDNF in Central Motor Structures and Motor Diseases

Brain-derived neurotrophic factor (BDNF), belonging to the neurotrophic family of growth factors, has a widespread distribution in the central and peripheral nervous systems. In central motor structures including the motor cortex, cerebellum, basal ganglia, and spinal cord, BDNF exerts both neurotrophic and direct electrophysiological effects via a high-affinity tyrosine receptor kinase B receptor and a common low-affinity p75 neurotrophin receptor. The underlying signaling pathways mainly involve mitogen-activated protein kinase cascades, phosphatidylinositol 3-kinase pathway, and phospholipase C-γ pathway. The loss of BDNF usually leads to neurodegeneration in these motor centers and eventually results in several severe motor diseases, such as amyotrophic lateral sclerosis, spinocerebellar ataxias, Parkinson’s disease, Huntington’s disease, as well as vestibular syndrome. In this review, we summarize the recent understanding of functions of BDNF in motor structures and suggest that BDNF may be a potent candidate for the treatment of these neurodegenerative motor diseases.     

Nonsomatotopic Organization of the Higher Motor Centers in Octopus

Hyperredundant limbs with a virtually unlimited number of degrees of freedom (DOFs) pose a challenge for both biological and computational systems of motor control. In the flexible arms of the octopus, simplification strategies have evolved to reduce the number of controlled DOFs [1], [2] and [3]. Motor control in the octopus nervous system is hierarchically organized [4] and [5]. A relatively small central brain integrates a huge amount of visual and tactile information from the large optic lobes and the peripheral nervous system of the arms [6], [7], [8] and [9] and issues commands to lower motor centers controlling the elaborated neuromuscular system of the arms. This unique organization raises new questions on the organization of the octopus brain and whether and how it represents the rich movement repertoire. We developed a method of brain microstimulation in freely behaving animals and stimulated the higher motor centers—the basal lobes—thus inducing discrete and complex sets of movements. As stimulation strength increased, complex movements were recruited from basic components shared by different types of movement. We found no stimulation site where movements of a single arm or body part could be elicited. Discrete and complex components have no central topographical organization but are distributed over wide regions.     

The Role of Nucleus Accumbens Core/Shell in Sleep-Wake Regulation and their Involvement in Modafinil-Induced Arousal

Background

We have previously shown that modafinil promotes wakefulness via dopamine receptor D₁ and D₂ receptors; however, the locus where dopamine acts has not been identified. We proposed that the nucleus accumbens (NAc) that receives the ventral tegmental area dopamine inputs play an important role not only in reward and addiction but also in sleep-wake cycle and in mediating modafinil-induced arousal.

Methodology/Principal Findings

In the present study, we further explored the role of NAc in sleep-wake cycle and sleep homeostasis by ablating the NAc core and shell, respectively, and examined arousal response following modafinil administration. We found that discrete NAc core and shell lesions produced 26.5% and 17.4% increase in total wakefulness per day, respectively, with sleep fragmentation and a reduced sleep rebound after a 6-hr sleep deprivation compared to control. Finally, NAc core but not shell lesions eliminated arousal effects of modafinil.

Conclusions/Significance

These results indicate that the NAc regulates sleep-wake behavior and mediates arousal effects of the midbrain dopamine system and stimulant modafinil.     

Stochastic Modeling of Mouse Motor Activity under Deep Brain Stimulation: The Extraction of Arousal Information

In the present paper, we quantify, with a rigorous approach, the nature of motor activity in response to Deep Brain Stimulation (DBS), in the mouse. DBS is currently being used in the treatment of a broad range of diseases, but its underlying principles are still unclear. Because mouse movement involves rapidly repeated starting and stopping, one must statistically verify that the movement at a given stimulation time was not just coincidental, endogenously-driven movement. Moreover, the amount of activity changes significantly over the circadian rhythm, and hence the means, variances and autocorrelations are all time varying. A new methodology is presented. For example, to discern what is and what is not impacted by stimulation, velocity is classified (in a time-evolving manner) as being zero-, one- and two-dimensional movement. The most important conclusions of the paper are: (1) (DBS) stimulation is proven to be truly effective; (2) it is two-dimensional (2-D) movement that strongly differs between light and dark and responds to stimulation; and, (3) stimulation in the light initiates a manner of movement, 2-D movement, that is more commonly seen in the (non-stimulated) dark. Based upon these conclusions, it is conjectured that the above patterns of 2-D movement could be a straightforward, easy to calculate correlate of arousal. The above conclusions will aid in the systematic evaluation and understanding of how DBS in CNS arousal pathways leads to the activation of behavior.     

The Role of Neurotransmitters and Proteins in the Genetic-Functional Organization of the Animal Brain

It was shown that animals that differ in behavioral characteristics (August and Wistar rats) also differ in neurotransmitter and protein metabolism, which can be considered as tests that adequately reflect the functional condition of the central nervous system. These differences are expressed at the level of both subcortical structures (the hippocampus and caudate nucleus) and various morphofunctional types of the sensorimotor cortex neurons (layers III and V). Studies on genetically different animals strains have revealed metabolic features that allow the determination of individual behavioral features and an estimation of individual brain structures in these processes.     

Causal Hierarchy within the Thalamo-Cortical Network in Spike and Wave Discharges

Background

Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges.

Methodology and Principal Findings

We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1.

Conclusion

Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy.     

The Organization and Role Of an Amateur Archeological Society

Abstract

The roles and functions of amateur archeologists and archeological societies are critically assayed in constructive terms.

A lot of ink has been spilled recently about “amateurs”, “pothunters”, “professionals”, “nonprofessionals”, and the like, on the pages of American Antiquity, the Plains Anthropologist and other publications. There is no question whatsoever that many professional archeologists have had unpleasant experiences with nonprofessionals, but my opinion is that the current published comments are doing little to help the situation. I object, not from the standpoint of a nonprofessional archeologist, which I am--one whose feelings have been hurt--but from the standpoint of one who is seriously interested in improving the situation.     

Self-Initiated Motor Behavioral Act-Related Neuronal Activity in the Cat Locus Coeruleus

In experiments on awake cats, we recorded the activity of 61 putative noradrenergic neurons localized within the region of the locus coeruleus (LC) of the brainstem. The animals were trained to perform a self-initiated (voluntary) motor act aimed at obtaining a food reward by pushing a pedal by the forelimb. The intervals between pushings (stay of the limb on a platform before initiation of the movement) should not be shorter than 4 sec, and the duration of the movement itself should not exceed 1 sec. The following impulse reactions were most clearly manifested (i) related to the pre-starting events and performance of the voluntary movement, (ii) related to the presentations of the conditioning stimuli, which predicted giving out the food reward (a positive signal) or the absence of the latter (a negative signal) and (iii) related to the reward presentation. About 50% of the LC units under study had changed their activities before the movement was initiated. These reactions can be related to a cognitive component (determination of the movement initiation(, which is present in the experimental task. Most neurons responded by phasic activation to presentation of the conditioning signals, and this activation was more pronounced in the case of negative signals. Responses of the studied nerve cells are probably indicative of the involvement of the LC neuronal systems in the perception of the emotiogenic stimuli, as well as in the processes providing the maintenance of selective attention within different stages of targeted behavioral acts.     

NO/cGMP Signaling and the Flexible Organization of Motor Behavior in Crustaceans

The basic elements of the NO/cGMP signaling pathway have beenidentified in the nervous systems of animals from nearly allof the major phyla. In crustaceans, the NO/cGMP pathway is associatedwith certain fundamental neuronal processes, including sensoryintegration and the organization and production of motor behavior.Here I review the evidence for NO synthesis and action in crustaceanneural networks, with an emphasis on the rhythmic motor circuitsof the crab stomatogastric ganglion (STG). In the STG, NO appearsto be released as an orthograde transmitter from descendingprojection neurons. NO's receptor, a cytopasmic isoform of guanylatecyclase (sGC), is expressed in a subset of the cells that participatein the gastric mill and pyloric central pattern generating networks.In spontaneously-active, in vitro preparations of the STG, pharmacologicalinhibitors of the NO/cGMP pathway cause the two rhythmic motorpatterns to collapse into a single conjoint rhythm. Parallelmotor output is restored when the ganglion is returned to normalsaline. Although precise mechanisms have yet to be determined,these data suggest that NO and cGMP play an important role inthe functional organization of STG networks. The STG, as wellas other crustacean models, provides a promising context forstudying the physiological and behavioral aspects of NO-mediatedsignaling in the nervous system.