Neural network mechanisms underlying stimulus driven variability reduction

It is well established that the variability of the neural activity across trials, as measured by the Fano factor, is elevated. This fact poses limits on information encoding by the neural activity. However, a series of recent neurophysiological experiments have changed this traditional view. Single cell recordings across a variety of species, brain areas, brain states and stimulus conditions demonstrate a remarkable reduction of the neural variability when an external stimulation is applied and when attention is allocated towards a stimulus within a neuron's receptive field, suggesting an enhancement of information encoding. Using an heterogeneously connected neural network model whose dynamics exhibits multiple attractors, we demonstrate here how this variability reduction can arise from a network effect. In the spontaneous state, we show that the high degree of neural variability is mainly due to fluctuation-driven excursions from attractor to attractor. This occurs when, in the parameter space, the network working point is around the bifurcation allowing multistable attractors. The application of an external excitatory drive by stimulation or attention stabilizes one specific attractor, eliminating in this way the transitions between the different attractors and resulting in a net decrease in neural variability over trials. Importantly, non-responsive neurons also exhibit a reduction of variability. Finally, this reduced variability is found to arise from an increased regularity of the neural spike trains. In conclusion, these results suggest that the variability reduction under stimulation and attention is a property of neural circuits.     

Neural mechanisms underlying amblyopia.

The nature of the neural basis of amblyopia is a matter of some debate. Recent neurophysiological data show correlates of amblyopia in the spatial properties of neurons in primary visual cortex. These neuronal deficits are probably the initial manifestation of the visual loss, but there are almost certainly additional deficits at higher levels of the visual pathways.     

Neural mechanisms underlying the evolvability of behaviour

The complexity of nervous systems alters the evolvability of behaviour. Complex nervous systems are phylogenetically constrained; nevertheless particular species-specific behaviours have repeatedly evolved, suggesting a predisposition towards those behaviours. Independently evolved behaviours in animals that share a common neural architecture are generally produced by homologous neural structures, homologous neural pathways and even in the case of some invertebrates, homologous identified neurons. Such parallel evolution has been documented in the chromatic sensitivity of visual systems, motor behaviours and complex social behaviours such as pair-bonding. The appearance of homoplasious behaviours produced by homologous neural substrates suggests that there might be features of these nervous systems that favoured the repeated evolution of particular behaviours. Neuromodulation may be one such feature because it allows anatomically defined neural circuitry to be re-purposed. The developmental, genetic and physiological mechanisms that contribute to nervous system complexity may also bias the evolution of behaviour, thereby affecting the evolvability of species-specific behaviour.     

Neural mechanisms underlying sex-specific behaviors in vertebrates

From invertebrates to humans, males and females of a given species display identifiable differences in behaviors, mostly but not exclusively pertaining to sexual and social behaviors. Within a species, individuals preferentially exhibit the set of behaviors that is typical of their sex. These behaviors include a wide range of coordinated and genetically pre-programmed social and sexual displays that ensure successful reproductive strategies and the survival of the species. What are the mechanisms underlying sex-specific brain function? Although sexually dimorphic behaviors represent the most extreme examples of behavioral variability within a species, the basic principles underlying the sex specificity of brain activity are largely unknown. Moreover, with few exceptions, the quest for fundamental differences in male and female brain structures and circuits that would parallel that of sexual behaviors and peripheral organs has so far uncovered modest quantitative rather than the expected clear qualitative differences. As will be detailed in this review, recent advances have directly challenged the established notion of the unique role of steroid hormones in organizing and activating male- and female-specific brain circuits and have uncovered new mechanisms underlying the neural control of sex-specific behaviors.     

Neural mechanisms underlying motivation of mental versus physical effort

Mental and physical efforts, such as paying attention and lifting weights, have been shown to involve different brain systems. These cognitive and motor systems, respectively, include cortical networks (prefronto-parietal and precentral regions) as well as subregions of the dorsal basal ganglia (caudate and putamen). Both systems appeared sensitive to incentive motivation: their activity increases when we work for higher rewards. Another brain system, including the ventral prefrontal cortex and the ventral basal ganglia, has been implicated in encoding expected rewards. How this motivational system drives the cognitive and motor systems remains poorly understood. More specifically, it is unclear whether cognitive and motor systems can be driven by a common motivational center or if they are driven by distinct, dedicated motivational modules. To address this issue, we used functional MRI to scan healthy participants while performing a task in which incentive motivation, cognitive, and motor demands were varied independently. We reasoned that a common motivational node should (1) represent the reward expected from effort exertion, (2) correlate with the performance attained, and (3) switch effective connectivity between cognitive and motor regions depending on task demand. The ventral striatum fulfilled all three criteria and therefore qualified as a common motivational node capable of driving both cognitive and motor regions of the dorsal striatum. Thus, we suggest that the interaction between a common motivational system and the different task-specific systems underpinning behavioral performance might occur within the basal ganglia.     

Neural mechanism underlying depressive-like state associated with social status loss

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Neural mechanisms and computations underlying stress effects on learning and memory

Stress has complex effects on memory function that can vary depending on the type of information that is learned and in relation to inter-individual characteristics. Recent work has also shown that stress can switch performance between memory systems, biasing it toward habit in detriment of spatial or goal-directed strategies. In addition, novel synaptic mechanisms have been implicated in the effects of stress in plasticity and memory. Computational modeling is emerging as a useful approach to integrate and to ascertain neural and cognitive computations underlying different effects of stress in memory. Having provided novel explanations for the inverted-U-shaped relationship between stress and cognitive performance, model-based analysis studies can improve our understanding of diverse effects of stress in cognition and psychopathology.     

Neural and psychological mechanisms underlying appetitive learning: links to drug addiction

The complexity of drug addiction mirrors the complexity of the psychological processes that motivate animals to work for any reinforcer, be it a natural reward or a drug. Here, we review the role of the nucleus accumbens, together with its dopaminergic and cortical innervation, in responding to reinforcement. One important contribution made by the nucleus accumbens is to the process through which neutral stimuli, once paired with a reinforcer such as a drug, have the capacity to motivate behaviour. This process may be one of several contributing to addiction, and it may be amenable to pharmacological intervention.     

Neural and hydroxyl radical mechanisms underlying laryngeal airway hyperreactivity induced by laryngeal acid-pepsin insult in anesthetized rats.

Laryngopharyngeal or gastroesophageal reflux is associated with laryngeal airway hyperreactivity (LAH), but neither the cause-effect relationship nor the underlying mechanism has been elucidated. Here we established a rat model with enhanced laryngeal reflex reactivity induced by laryngeal acid-pepsin insult and investigated the neural and hydroxyl radical (*OH) mechanisms involved. The laryngeal segments of 103 anesthetized rats were functionally isolated while animals breathed spontaneously. Ammonia vapor was delivered into the laryngeal segment to measure laryngeal reflex reactivity. We found that the laryngeal pH 5-pepsin treatment doubled the reflex apneic response to ammonia, whereas laryngeal pH 7.4-pepsin, pH 2-pepsin, and pH 5-denatured pepsin treatment had no effect. Histological examination revealed limited laryngeal inflammation and epithelial damage after pH 5-pepsin treatment and more severe damage after pH 2-pepsin treatment. In rats that had received the laryngeal pH 5-pepsin treatment, the apneic response to ammonia was abolished by either denervation or perineural capsaicin treatment (PCT; a procedure that selectively blocks capsaicin-sensitive afferent fibers) of the superior laryngeal nerves, but was unaffected by perineural sham treatment. LAH was prevented by laryngeal application of either dimethylthiourea (DMTU; a *OH scavenger) or deferoxamine (DEF; an antioxidant for *OH), but was unaltered by the DMTU vehicle or iron-saturated DEF (ineffective DEF). LAH reappeared after recovery from PCT, DMTU, or DEF treatment. We conclude that 1) laryngeal insult by pepsin at a weakly acidic pH, but not at acidic pH, can produce LAH; and 2) LAH is probably mediated through sensitization of the capsaicin-sensitive laryngeal afferent fibers by a *OH mechanism.     

Review. Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction

We hypothesize that drug addiction can be viewed as the endpoint of a series of transitions from initial voluntary drug use through the loss of control over this behaviour, such that it becomes habitual and ultimately compulsive. We describe evidence that the switch from controlled to compulsive drug seeking represents a transition at the neural level from prefrontal cortical to striatal control over drug-seeking and drug-taking behaviours as well as a progression from ventral to more dorsal domains of the striatum, mediated by its serially interconnecting dopaminergic circuitry. These neural transitions depend upon the neuroplasticity induced by chronic self-administration of drugs in both cortical and striatal structures, including long-lasting changes that are the consequence of toxic drug effects. We further summarize evidence showing that impulsivity, a spontaneously occurring behavioural tendency in outbred rats that is associated with low dopamine D2/3 receptors in the nucleus accumbens, predicts both the propensity to escalate cocaine intake and the switch to compulsive drug seeking and addiction.     

Neural mechanisms for hedonistic behavior

Some neural mechanisms are described which interpret neurobiophysically the determination of the behavior of an individual by the maximizing of his satisfaction, or pleasure.     

Neural driven angiogenesis by overexpression of nerve growth factor

Mechanisms regulating angiogenesis are crucial in adjusting tissue perfusion on metabolic demands. We demonstrate that overexpression of nerve growth factor (NGF) in brown adipose tissue (BAT) of NGF-transgenic mice elevates both mRNA and protein levels of vascular endothelial growth factor (VEGF) and VEGF-receptors. Increased vascular permeability, leukocyte–endothelial interactions (LEI), and tissue perfusion were measured using intravital microscopy. NGF-stimulation of adipocytes and endothelial cells elevates mRNA expression of VEGF and its receptors, an effect blocked by NGF neutralizing antibodies. These data suggest an activation of angiogenesis as a result of both: stimulation of adipozytes and direct mitogenic effects on endothelial cells. The increased nerve density associated with vessels strengthened our hypothesis that tissue perfusion is regulated by neural control of vessels and that the interaction between the NGF and VEGF systems is the critical driver for the activated angiogenic process. The interaction of VEGF- and NGF-systems gives new insights into neural control of organ vascularization and perfusion.     

Ionic transport mechanisms underlying fluid secretion by the pancreas

The pancreas is a 'leaky' epithelium and secretes a juice in which sodium and potassium have concentrations similar to those of plasma. The characteristic features of the secretion are its isosmolality and its high bicarbonate concentration. It is the latter that has attracted considerable attention. Secretion in the isolated cat pancreas is directly proportional to the bicarbonate concentration in the nutrient fluid. The ability of the gland to secrete weak acids has led to the view that because of the very different chemical nature of the anions, it is most likely that it is a component common to all buffers, the proton, that is subject to active transport. This is supported by the decrease in pH and the increase in rho CO2 of the venous effluent when secretion occurs and the sensitivity of secretion to the pH of the nutritional extracellular fluid. It is proposed that the cellular mechanisms are as follows: CO2 diffuses into the cell and is hydrated to carbonic acid under the influence of carbonic anhydrase. The bicarbonate ion so formed diffused into the ductular lumen and the proton is transported backwards through the epithelium with a proton pump (Mg2+ -ATPase) provisionally located in the luminal membrane and a hydrogen-sodium exchange carrier located in the basolateral membrane. Energy for the latter process is derived from the sodium gradient between extracellular fluid and cell. This gradient is maintained by a (Na+ + K+)-ATPase also located in the basolateral membrane. Chloride appears to be transported partly through a chloride-bicarbonate exchange mechanism but largely passively together with a large sodium and potassium component through the paracellular pathway. Osmotic equilibrium is likely to occur in the small ductules.     

Promising high monetary rewards for future task performance increases intermediate task performance

In everyday life contexts and work settings, monetary rewards are often contingent on future performance. Based on research showing that the anticipation of rewards causes improved task performance through enhanced task preparation, the present study tested the hypothesis that the promise of monetary rewards for future performance would not only increase future performance, but also performance on an unrewarded intermediate task. Participants performed an auditory Simon task in which they responded to two consecutive tones. While participants could earn high vs. low monetary rewards for fast responses to every second tone, their responses to the first tone were not rewarded. Moreover, we compared performance under conditions in which reward information could prompt strategic performance adjustments (i.e., when reward information was presented for a relatively long duration) to conditions preventing strategic performance adjustments (i.e., when reward information was presented very briefly). Results showed that high (vs. low) rewards sped up both rewarded and intermediate, unrewarded responses, and the effect was independent of the duration of reward presentation. Moreover, long presentation led to a speed-accuracy trade-off for both rewarded and unrewarded tones, whereas short presentation sped up responses to rewarded and unrewarded tones without this trade-off. These results suggest that high rewards for future performance boost intermediate performance due to enhanced task preparation, and they do so regardless whether people respond to rewards in a strategic or non-strategic manner.