Trevor W. Robbins

Bio: Trevor W. Robbins is an academic researcher from University of Cambridge. The author has contributed to research in topics: Prefrontal cortex & Impulsivity. The author has an hindex of 231, co-authored 1137 publications receiving 164437 citations. Previous affiliations of Trevor W. Robbins include Centre national de la recherche scientifique & Massachusetts Institute of Technology.

Dopaminergic and serotonergic function following isolation rearing in rats: study of behavioural responses and postmortem and in vivo neurochemistry.

Abstract: This series of experiments compared isolation-reared and socially reared rats for their locomotor activity, behavioural stereotypy, and monoamine function both postmortem and in vivo using intracerebral dialysis In Experiment 1, isolates showed an altered time course of locomotor activity following d-amphetamine sulphate (AMPH) administration (05, 20, 30, or 50 mg/kg, SC) Isolation-reared rats also showed increased sensitivity to the sedative effects of a low dose of apomorphine hydrochloride (01 mg/kg) but did not differ from social controls following higher doses of the drug (05, 15, or 30 mg/kg, SC) Isolates showed a decrease in the intensity of apomorphine-induced stereotyped behaviours but no change in stereotypy induced by AMPH In Experiment 2, isolates had higher postmortem dopamine (DA) concentrations and an altered asymmetry in DA function in the medial prefrontal cortex (PFC) but not in the nucleus accumbens (NAC) or caudate putamen (CPu) Isolated rats also had a lower 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratio in the NAC (but not in the PFC or CPu) compared to controls Experiment 3 used intracerebral dialysis to examine monoamine function in vivo following isolation rearing Isolates showed greater increases in extracellular DA and greater decreases in DOPAC in response to 2 mg/kg AMPH SC in both the NAC and CPu There were no apparent differences in the perfusate concentrations of either dopamine (DA), dihydroxyphenylacetic acid (DOPAC), or homovanillic acid (HVA) prior to drug administration However, consistent with the results of Experiment 2, isolates had a reduced basal perfusate concentration of 5-HIAA from the NAC but not from the CPu Experiment 4 measured postsynaptic DA function in CPu tissue slices following isolation Isolation rearing did not affect cAMP accumulation in response to stimulation of D1 DA receptors by DA (0, 27, 9, or 30 microM) In addition, isolation rearing did not affect the coupling between D1 and D2 receptors, as measured by the increase in cAMP accumulation with 1 microM 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepin (SK&F 38393) and its reduction by 10 microM quinperole hydrochloride (LY 171555) These results are discussed in terms of the possible relationship between these neurochemical findings and the behavioural disturbances following isolation rearing of rats

Prefrontal serotonin depletion affects reversal learning but not attentional set shifting

Abstract: Recently, we have shown that serotonin (5-HT) depletion from the prefrontal cortex (PFC) of the marmoset monkey impairs performance on a serial discrimination reversal (SDR) task, resulting in perseverative responding to the previously correct stimulus (Clarke et al., 2004). This pattern of impairment is just one example of inflexible responding seen after damage to the PFC, with performance on the SDR task being dependent on the integrity of the orbitofrontal cortex. However, the contribution of 5-HT to other forms of flexible responding, such as attentional set shifting, an ability dependent on lateral PFC (Dias et al., 1996a), is unknown. The present study addresses this issue by examining the effects of 5,7-dihydroxytryptamine-induced PFC 5-HT depletions on the ability to shift attention between two perceptual dimensions of a compound visual stimulus (extradimensional shift). Monkeys with selective PFC 5-HT lesions, despite being impaired in their ability to reverse a stimulus-reward association, were unimpaired in their ability to make an extradimensional shift when compared with sham-operated controls. These findings suggest that 5-HT is critical for flexible responding at the level of changing stimulus-reward contingencies but is not essential for the higher-order shifting of attentional set. Thus, psychological functions dependent on different loci within the PFC are differentially sensitive to serotonergic modulation, a finding of relevance to our understanding of cognitive inflexibility apparent in disorders such as obsessive-compulsive disorder and schizophrenia.

Functional studies of the central catecholamines.

Abstract: Publisher Summary This chapter describes the mesencephalic dopamine (DA) system, the lateral tegmental noradrenergic system, the locus ceruleus noradrenergic system, and noradrenergic-dopaminergic interactions. It discusses the respective roles of the catecholamine systems, and discusses how they might interact to mediate arousal and activational processes. DA neurons innervating the forebrain are found in the mesencephalic tegmentum, forming a bilateral crescentic cluster of cell bodies. The effects of microinjections of DA or d-amphetamine into the nucleus accumbens clearly support the hypothesis that increases in locomotion depend on DA receptors there. Thus, the subject of functional communication between noradrenergic and dopaminergic systems is one that cannot be unambiguously pronounced upon. However, there would appear to be sufficient behavioral, neuroanatomical, neurochemical, and pharmacological evidence to justify considerable effort in discerning the relationship between them, as this may considerably inform the current understanding of the control mechanisms underlying many forms of behavior.

Cognitive Inflexibility after Prefrontal Serotonin Depletion Is Behaviorally and Neurochemically Specific

Abstract: We have previously demonstrated that prefrontal serotonin depletion impairs orbitofrontal cortex (OFC)-mediated serial discrimination reversal (SDR) learning but not lateral prefrontal cortex (PFC)mediated attentional set shifting. To address the neurochemical specificity of this reversal deficit, Experiment 1 compared the effects of selective serotonin and selective dopamine depletions of the OFC on performance of the SDR task. Whereas serotonin depletions markedly impaired performance, OFC dopamine depletions were without effect. The behavioral specificity of this reversal impairment was investigated in Experiment 2 by examining the effect of OFC serotonin depletion on performance of a modified SDR task designed to distinguish between 3 possible causes of the impairment. The results showed that the reversal deficit induced by prefrontal serotonin depletion was not due to a failure to approach a previously unrewarded stimulus (enhanced learned avoidance) or reduced proactive interference. Instead, it was due specifically to a failure to inhibit responding to the previously rewarded stimulus. The neurochemical and behavioral specificity of this particular form of cognitive inflexibility is of particular relevance to our understanding of the aetiology and treatment of inflexible behavior apparent in many neuropsychiatric and neurodegenerative disorders involving the PFC.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Control of goal-directed and stimulus-driven attention in the brain

Abstract: We review evidence for partially segregated networks of brain areas that carry out different attentional functions. One system, which includes parts of the intraparietal cortex and superior frontal cortex, is involved in preparing and applying goal-directed (top-down) selection for stimuli and responses. This system is also modulated by the detection of stimuli. The other system, which includes the temporoparietal cortex and inferior frontal cortex, and is largely lateralized to the right hemisphere, is not involved in top-down selection. Instead, this system is specialized for the detection of behaviourally relevant stimuli, particularly when they are salient or unexpected. This ventral frontoparietal network works as a 'circuit breaker' for the dorsal system, directing attention to salient events. Both attentional systems interact during normal vision, and both are disrupted in unilateral spatial neglect.

An integrative theory of prefrontal cortex function

Abstract: ▪ Abstract The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed

Chapter 11 Working memory

Abstract: Publisher Summary This chapter focuses on the modern notion of short-term memory, called working memory. Working memory refers to the temporary maintenance of information that was just experienced or just retrieved from long-term memory but no longer exists in the external environment. These internal representations are short-lived, but can be maintained for longer periods of time through active rehearsal strategies, and can be subjected to various operations that manipulate the information in such a way that makes it useful for goal-directed behavior. Working memory is a system that is critically important in cognition and seems necessary in the course of performing many other cognitive functions, such as reasoning, language comprehension, planning, and spatial processing. This chapter demonstrates the functional importance of dopamine to working memory function in several ways. Elucidation of the cognitive and neural mechanisms underlying human working memory is an important focus of cognitive neuroscience and neurology for much of the past decade. One conclusion that arises from research is that working memory, a faculty that enables temporary storage and manipulation of information in the service of behavioral goals, can be viewed as neither a unitary, nor a dedicated system. Data from numerous neuropsychological and neurophysiological studies in animals and humans demonstrates that a network of brain regions, including the prefrontal cortex, is critical for the active maintenance of internal representations.