Mark Tricklebank

Mark Tricklebank
King's College London | KCL · Department of Neuroimaging

BSc,MSc,DSc PhD FBPS

About

209
Publications
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Publications

Publications (209)
Preprint
Full-text available
Working memory enables incorporation of recent experience into subsequent decision-making. This processing recruits both prefrontal cortex and hippocampus, where neurons encode task cues, rules and outcomes. However, precisely which information is carried when, and by which neurons, remains unclear. Using population decoding of activity in rat medi...
Article
Depression is the world’s predominant mental health problem and a leading cause of disability. Neuropharmacological research has not yet advanced treatments to sufficiently meet clinical need, largely due to the failure of animal models to predict clinical efficacy. The forced swim test (FST) has been extensively used in the field of antidepressant...
Article
Full-text available
Background There is urgent need for new medications for psychiatric disorders. Mental illness is expected to become the leading cause of disability worldwide by 2030. Yet, the last two decades have seen the pharmaceutical industry withdraw from psychiatric drug discovery after costly late-stage trial failures in which clinical efficacy predicted pr...
Book
An uptodate review of our knowledge of thePhysiology and pharmacology of the serotoninsystem
Article
Full-text available
In an uncertain world, the ability to predict and update the relationships between environmental cues and outcomes is a fundamental element of adaptive behaviour. This type of learning is typically thought to depend on prediction error, the difference between expected and experienced events and in the reward domain that has been closely linked to m...
Preprint
Full-text available
In an uncertain world, the ability to predict and update the relationships between environmental cues and outcomes is a fundamental element of adaptive behaviour. This type of learning is typically thought to depend on prediction error, the difference between expected and experienced events, and in the reward domain this has been closely linked to...
Chapter
Serotonergic hallucinogens produce alterations of perceptions, mood, and cognition, and have putative anxiolytic, antidepressant, and antiaddictive properties. There are many sources of compounds which act as serotonin agonist hallucinogens and psychedelics. Studies in experimental animals and ex vivo have provided strong evidence for the involveme...
Article
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Understanding brain function at the cell and circuit level requires representation of neuronal activity through multiple recording sites and at high sampling rates. Traditional tethered recording systems restrict movement and limit the environments suitable for testing, while existing wireless technology is still too heavy for extended recording in...
Article
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Most in vivo models of ischaemic stroke target the middle cerebral artery and a spectrum of stroke severities, from mild to substantial, can be achieved. This review describes opportunities to improve the in vivo modelling of ischaemic stroke and animal welfare. It provides a number of recommendations to minimise the level of severity in the most c...
Article
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Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the ‘respons...
Article
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Nearly all Pharmaceutical companies have withdrawn from Psychiatric Drug Discovery a time when clinical need for new medications is at an all time high.The authors posit that things are not as bad as they seem but resources must be made available again before the skilled infrastructure is lost
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Despite the vast amount of research on schizophrenia and depression in the past two decades, there have been few innovative drugs to treat these disorders. Precompetitive research collaborations between companies and academic groups can help tackle this innovation deficit, as illustrated by the achievements of the IMI-NEWMEDS consortium.
Article
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A chromosomal microdeletion at the 22q11.2 locus is associated with extensive cognitive impairments, schizophrenia and other psychopathology in humans. Previous reports indicate that mouse models of the 22q11.2 microdeletion syndrome (22q11.2DS) may model the genetic basis of cognitive deficits relevant for neuropsychiatric disorders such as schizo...
Article
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A chromosomal microdeletion at the 22q11.2 locus is associated with extensive cognitive impairments, schizophrenia and other psychopathology in humans. Previous reports indicate that mouse models of the 22q11.2 microdeletion syndrome (22q11.2DS) may model the genetic basis of cognitive deficits relevant for neuropsychiatric disorders such as schizo...
Article
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Reversal learning requires associative learning and executive functioning to suppress non-adaptive responding. Reversal-learning deficits are observed in e.g. schizophrenia and obsessive-compulsive disorder and implicate neural circuitry including the orbitofrontal cortex (OFC). Serotonergic function has been strongly linked to visual reversal lear...
Article
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Validating preclinical biomarkers that predict treatment efficacy remains a critical imperative for neuropsychiatric drug discovery. With the establishment of novel in vivo imaging methods, it has become possible to think how such translational proof-of-concept studies may look. The aim of this study was to use in vivo oxygen (O2) amperometry to si...
Article
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While treatment options are available, excessive daytime sleepiness (EDS) remains a significant unmet medical need for many patients. Relatively little rodent behavioural pharmacology has been conducted in this context to assess potential pro-vigilant compounds for their ability to restore functional capacity following experimentally induced sleep...
Article
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Adult rats exposed to methylazoxymethanol acetate (MAM) at embryonic day 17 (E17) display robust pathological alterations in the hippocampus. However, discrepancies exist in the literature regarding the behavioural effects of this pre-natal manipulation. Therefore, a systematic assessment of MAM E17-induced behavioural alterations was conducted usi...
Article
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While resting-state functional magnetic resonance imaging can probe intrinsic network connectivity in both human and rodent brain, behavioral modulation of these connectivity patterns has not yet been demonstrated in the rodent due to the requirements of immobilization or anesthesia for MRI scanning. To enable the effects of behavioral tasks on fun...
Article
There is substantial interest in the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine in psychiatric research, as it exerts psychotomimetic and antidepressant effects in rodents and humans. Here we investigated proteomic changes in brain and serum after acute treatment of rats with ketamine using two targeted proteomic profiling methods. Mu...
Article
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Typical and atypical antipsychotics have been shown to alleviate N-methyl-D-aspartate (NMDA) receptor antagonist-induced BOLD signals in healthy humans and animals to differing degrees; factors that might relate to their different molecular mechanisms and clinical profiles. Recent studies have also extended these investigations to the analysis of r...
Article
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Using environmental cues for the prediction of future events is essential for survival. Such cue-outcome associations are thought to depend on mesolimbic circuitry involving the nucleus accumbens (NAc) and prefrontal cortex (PFC). Several studies have identified roles for both NAc and PFC in the expression of stable goal-directed behaviors, but muc...
Article
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Memory deficits associated with hippocampal dysfunction are a key feature of a number of neurodegenerative and psychiatric disorders. The discrete-trial rewarded alternation T-maze task is highly sensitive to hippocampal dysfunction. Normal mice have spontaneously high levels of alternation, whereas hippocampal-lesioned mice are dramatically impair...
Article
Introduction Performance effects of sleep restriction are generally assessed across three broad domains: cognitive performance, motor performance and mood. Within the domain of cognition, the psychomotor vigilance task (PVT) provides a means to assess vigilant attentional capacity with low cognitive demand, allowing robust deficits following sleep...
Article
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We previously reported involvement of right prefrontal cholinergic activity in veridical signal detection. Here, we first recorded real-time acetylcholine release in prefrontal cortex (PFC) during specific trial sequences in rats performing a task requiring signal detection as well as rejection of nonsignal events. Cholinergic release events record...
Article
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There are many new advances in neuroscience and mental health which should lead to a greater understanding of the neurobiological dysfunction in neuropsychiatric disorders and new developments for early, effective treatments. To do this, a biomarker approach combining genetic, neuroimaging, cognitive and other biological measures is needed. The aim...
Article
Non-competitive N-methyl-d-aspartate receptor (NMDAR) antagonists such as phencyclidine (PCP) and ketamine are commonly and interchangeably used to model aspects of schizophrenia in animals. We compared here the effects of acute administration of these compounds over a range of pre-treatment times in tests of instrumental responding (VI 30s respons...
Article
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Lesion and electrophysiological studies in rodents have identified the amygdala and hippocampus (HPC) as key structures for Pavlovian fear conditioning, but human functional neuroimaging studies have not consistently found activation of these structures. This could be because hemodynamic responses cannot detect the sparse neuronal activity proposed...
Article
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Rhythmic neural network activity patterns are defining features of sleep, but interdependencies between limbic and cortical oscillations at different frequencies and their functional roles have not been fully resolved. This is particularly important given evidence linking abnormal sleep architecture and memory consolidation in psychiatric diseases....
Article
The demonstrated functional interaction of metabotropic glutamate 5 (mGlu(5)) receptors with N-methyl-d-aspartate (NMDA) receptors has prompted speculation that their activation may offer a potential treatment for aspects of schizophrenia. Development of selective mGlu(5) agonists has been difficult, but several different positive allosteric modula...
Article
Psychiatric drug discovery needs to close the systems neuroscience gap to improve the clinical success rates of candidate drugs with novel mechanisms of action.
Article
Real-time in vivo oxygen amperometry, a technique that allows measurement of regional brain tissue oxygen (O(2)) has been previously shown to bear relationship to the BOLD signal measured with functional magnetic resonance imaging (fMRI) protocols. In the present study, O(2) amperometry was applied to the study of reward processing in the rat nucle...
Article
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Neuronal activity elicits metabolic and vascular responses, during which oxygen is first consumed and then supplied to the tissue via an increase in cerebral blood flow. Understanding the spatial and temporal dynamics of blood and tissue oxygen (To₂) responses following neuronal activity is crucial for understanding the physiological basis of funct...
Article
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Based on the glutamatergic hypothesis of schizophrenia we assessed the effects of a novel mGlu5 positive allosteric modulator, LSN2463359 [N-(1-methylethyl)-5-(pyridin-4-ylethynyl)pyridine-2-carboxamide] on deficits in cognitive flexibility in two distinct rodent models of schizophrenia, the neurodevelopmental MAM E17 model and the acute PCP model....
Article
Cognitive testing with touchscreen-equipped operant boxes ('touchscreens') is becoming increasingly popular. Tasks, such as paired associate learning or reversal learning of visual stimuli, have the discrimination of visual stimuli as a fundamental component. However, the effect of drugs commonly used in the study of cognitive mechanisms has yet to...
Article
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Coordinated activity spanning anatomically distributed neuronal networks underpins cognition and mediates limbic-cortical interactions during learning, memory, and decision-making. We used CP55940, a potent agonist of brain cannabinoid receptors known to disrupt coordinated activity in hippocampus, to investigate the roles of network oscillations d...
Article
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Administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM) on embryonic day 17 (E17) produces behavioral and anatomical brain abnormalities, which model some aspects of schizophrenia. This has lead to the premise that MAM rats are a neurodevelopmental model for schizophrenia. However, the underlying molecular pathways affected in...
Article
Full-text available
The risk of developing schizophrenia has been linked to perturbations in embryonic development, but the physiological alterations that result from such insults are incompletely understood. Here, we have investigated aspects of hippocampal physiology in a proposed neurodevelopmental model of schizophrenia, induced during gestation in rats by injecti...
Article
Neuroanatomical, electrophysiological and behavioural abnormalities following timed prenatal methylazoxymethanol acetate (MAM) treatment in rats model changes observed in schizophrenia. In particular, MAM treatment on gestational day 17 (E17) preferentially disrupts limbic-cortical circuits, and is a promising animal model of schizophrenia. The hyp...
Article
Full-text available
N-methyl-D: -Aspartate receptor (NMDAR) antagonists such as ketamine induce cognitive symptoms in man similar to those of schizophrenia and therefore might be useful as models of the disease in animals. However, it is unclear which NMDAR antagonist(s) offer the best means to produce cognitive deficits in attention and working memory and to what ext...
Article
Cognitive dysfunction is core to schizophrenia, and remains poorly treated by existing therapies. A prominent hypothesis suggests that many symptoms arise from N-methyl-d-aspartate receptor (NMDAR) hypofunction. Subsequently, there has emerged a widespread use of many preclinical and clinical NMDAR antagonist models in the search for novel treatmen...
Article
Tissue O₂ can be monitored using a variety of electrochemical techniques and electrodes. In vitro and in vivo characterisation studies for O₂ reduction at carbon paste electrodes (CPEs) using constant potential amperometry (CPA) are presented. Cyclic voltammetry indicated that an applied potential of -650 mV is required for O₂ reduction at CPEs. Hi...