NIHRDataInsights/HRCSData huggingface dataset:
Title: Glial regulation of neural signalling in health and disease with an emphasis on understanding its possible role in psychotic-like states
Funder: Wellcome Trust

Abstract: Astrocytes respond to neurotransmitters released from neurons with a rise of [Ca2+]i. It is becoming increasingly clear that these [Ca2+]i rises can in turn evoke neurotransmitter release from astrocytes, which modulates neuronal function, and that microglial cells can regulate this signalling from astrocytes. We will use patch-clamping, calcium imaging and calcium uncaging in brain slices, to examine the following aspects of these newly discovered signalling pathways, which have been little studied and which may be relevant to understanding both the normal function of the CNS and the changes of function which lead to psychotic-like states. (1) How do the amine transmitters serotonin, dopamine and noradrenaline modulate astrocyte [Ca2+]i and thus synaptic currents in nearby neurons? (2) How do the main excitatory and inhibitory transmitters glutamate and GABA modulate astrocyte [Ca2+]i and thus synaptic currents in nearby neurons? (3) How do endocannabinoids modulate astrocyte [Ca2+]i and thus synaptic currents in nearby neurons? (4) How do agents known to induce psychotic-like states, such as amphetamine, LSD, ketamine and exogenous cannabinoids, modulate astrocyte [Ca2+]i and thus synaptic currents in nearby neurons? (5) What is the role of ATP and adenosine in the above phenomena? (6) How do microglia regulate this signalling?


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Mechanisms of grid cell processing: interactions at the network level
Funder: Wellcome Trust

Abstract: The primary goal of this project is to establish the role of cholinergic signalling in the modulation of grid cell firing patterns. In particular, to study the relationship between Acetylcholine concentration in the Entorhinal Cortex and grid scale. Acetylcholine is a putative signal of novelty and uncertainty, and has been shown to affect the theta-band frequency of grid cell oscillations in-vitro. In parallel, grid scale is known to increase in novel situations. As such, we aim to demonstrate a role for Acetylcholine and its effects on theta-firing as a mechanism underlying changes in grid scale during situations of novelty and uncertainty. Examination of the biological basis of the rodent cognitive map is perhaps themost promising available model system in which we can bridge the gap from behaviour and cognition to neurons and circuits. Understanding how spatial firing in the entorhinal cortex and hippocampus is generated and modified in novel environments would be an important extension of our knowledge of spatialcognition, and more generally to our understanding of the process of memory formation


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Investigating the sense of agency in human-computer interaction.
Funder: Wellcome Trust

Abstract: The proposed research is to investigate the sense of agency in human-computer interaction (HCI). The sense of agency is the experience of initiating and controlling actions in order to influence events in the environment. Agency is well studied from a cognitive neuroscientific perspective because it underlies many cognitive disorders such as schizophrenia and psychosis. HCI involves the study, planning and design of the interaction between humans and computers. Currently there is a paucity of research lookingat agency in the context of technology. However it is a hugely topical and relevant area. There are two key goals of this PhD project- 1) enhance our understanding of agency in various computer/machine interaction contexts, 2) highlight the key considerations regarding agency and control in HCI research.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Cortical mechanisms underlying human behavioural control.
Funder: Wellcome Trust

Abstract: Our brains devote substantial resources towards making profitable choices by often selecting courses of actions with high value, and seldom those with low value. The orbitofrontal cortex has been shown to represent an internal model of the world that allows it to make precise associations between stimuli and rewards and to flexibly guide a goal-oriented behaviour. The hippocampus also has a model of the environment, however it remains debatable if it is restricted to spatial representations only, or if it has a more general role. Interestingly, both of these brain areas have been shown, separately, to make very similar inferences that influence future behaviour. However, their interactions for guiding goal-oriented behaviour are not sufficiently understood. During my DPhil, I aim to study the interactions between the orbitofrontal cortex and the hippocampus using non-invasive human neuroimagingtechniques. My key goals are to dissociate between their functional roles and underlying mechanisms for making stimulus-stimulus and stimulus-reward associations and to explore how these associations are represented in the brain.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: The influence of spatial and temporal context on information integration during human decision-making.
Funder: Wellcome Trust

Abstract: Decisions often require integration of information from different sources. Integration and choice are shaped by the temporal and spatial context in whichinformation occurs. We propose a series of experiments involving behavioural and neurophysiological recordings that are aimed at characterising these contextual influences and pinpointing their neural substrates. The proposed experiments involve a new paradigm (the 'two streams' task) in which discretesamples of information are presented in two parallel streams, after which participants judge the relative information provided by each stream. Coupled with high-resolution imaging methods such as electroencephalography (EEG), magnetoencephalography (MEG), and functional magnetic resonance imaging (fMRI), and with formal modelling of the decision process, this will allow us to characterise how the processing of each new sample of information is modulated by information presented beforehand (temporal context) and in the opposing stream (spatial context). Neural recordings will allow us to identifythe brain regions were information processing is modulated, with a focus on the parietal and medial prefrontal cortices. We hypothesise that contextual influences on information integration arise from well-described phenomena in the cognitive science literature, such as perceptual priming, spatial attention, and conflict monitoring and resolution, and give rise to suboptimalbiases in decision-making.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Nonlinear modelling of courtship behaviour in Drosophila melanogaster.
Funder: Wellcome Trust

Abstract: The proposed research aims to develop mathematical models to help in understanding the relationship between genes, neuronal circuits, and behaviour. A nonlinear model of Drosophila courtship behaviour will be developed to guide experimental studies by providing testable predications about both neural activity and behaviour. Three projects are proposed, modelling different aspects of courtship. The first project aims to model courtship song, in particular switches between two modes of song: sine and pulse. It will be investigated whether switches in male song are related to locomotion changes in the female. The second project aims to develop and evaluate a model of courtship behaviour. A male fly courts a female by tapping, abdomen quivering, singing and licking. Switches between these behaviours seem random. A nonlinear model may account for these switches. A comprehensive computational model will be used to investigate the underlying neural basis of courtship in the fly. The third project aims to extend the model developed in the second project by including experience as a critical parameter. This bridges courtship and memory research in the fly and suggests the possibility of modulation of innate behaviour by individual experience.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Perspective distortion in 3D display systems
Funder: Wellcome Trust

Abstract: 3D displays are getting more and more mainstream. While qualitative depth perception is very well exploited in entertainment, quantitative depth perception requires additional information that is currently not provided in stereoscopic displays - knowing how far away and how big the objects of interest are in the displayed virtual world is essential for users in medicine, engineering and other industries. 3D vision in general is affected by a number of cues, of which only a limited number is restored by the current display technologies. Particularly, depth perception is largely affected by changes of perspective with the change of viewing angle: being able to freely 'look behind' an object enables the observers to form a much more accurate picture in their minds than just plainly seeing them from one angle. The goal of the PhD is to gain more understanding of this previously neglectedcue that enables us to have quantitative depth perception, with the use of available cutting-edge technology such as multi-projection display systems,augmented reality and integral displays.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Analysis of Trappc9 functions in brain development.
Funder: Wellcome Trust

Abstract: Recently, mutations in six genes have been identified to cause the neurodevelopmental disorder 'autosomal recessive non-syndromic mental retardation' in humans. 'Trafficking protein particle complex subunit 9' (Trappc9), also known as 'NIK and IKK? binding protein' (NIBP), is one of these genes, which leads to a range of symptoms when homozygously mutated, including microcephaly, corpus callosum and white matter abnormalities, speechimpairment and cognitive delay. The molecular basis of Trappc9's role in braindevelopment is not yet known. Some studies implicate Trappc9 in intracellular vesicle trafficking, while other work highlights a role in NF-?B signalling, promotion of neurite outgrowth and cell survival. Since no mouse model for the human disorder has been described so far, we aim to analyse the phenotype of a Trappc9 knock-out line with regard to neuron proliferation and cell survival, establishment of neuronal connections and potential physiological and/or behavioural abnormalities. We also aim to investigate the molecular basis of this disorder by using a range of molecularbiology techniques in PC12 cells and/or primary neurons (siRNA/lentivirus knock-down, NF-?B cytoplasmic-nuclear translocation studies), to clarify the mechanisms by which this protein exerts its functions. Is Trappc9 involved in NF-?B cytoplasmic-nuclear translocation, for example upon signalling from neurotrophin receptors?


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Neural network analysis using a novel multichannel "SMART" neuroprobe.
Funder: Wellcome Trust

Abstract: Neuroscience is entering an exciting period when it will be possible to decipher the neural codes underlying perception and cognition. Novel genetic, molecular, physiological, optical and behavioural approaches will allow the monitoring of activity across ensembles of neurons in behaving rodents, and the manipulation of this activity in a temporally and spatially precise manner. For the first time we will establish causal links between patterns of neural activity and behaviour, and carry out decisive tests of both new and long-standing hypotheses about the computational properties of neural circuits. Members of the consortia seek to understand thepatterns of neural activity underlying sensory, motor and cognitive representations, and the rules by which they are assembled. The core of the present proposal is the development and testing of a major stepchange in silicon-based electrode technology to rapidly accelerate the pace of this work by greatly increasing the simultaneous sampling of extracellular electrical signals within and across multiple brain regions.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: A multi-level analysis of the CA2 region of the hippocampus
Funder: Wellcome Trust

Abstract: The CA2 of hippocampus receives synaptic inputs from both entorhinal cortex, via temporoammonic fibres, and from the CA3, via Schaffer collateral fibres. Yet these synapses have not been studied in detail. I plan to examine the distinct plasticity properties of these two inputs to CA2, their roles in learning and memory, and their regulation by the Regulators of G-protein Signalling proteins RGS4 and RGS14, which are highly expressed in CA2. Key goals include: To use electrophysiological and optogenetic techniques to determine how RGS proteins regulate mGluR-dependent plasticity at the two major inputs to CA2. To use confocal microscopy methods to examine how spine size is regulated by RGS proteins and by mGluR-dependent synaptic plasticity and whether these differ between the two inputs to CA2. To determine how neuronal activation is controlled by RGS proteins using Arc as a measure. To examine how RGS proteins and mGluR plasticity regulate the function of CA2


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: A theoretical and experimental framework for relating endogenous brain fluctuations to human decision-making.
Funder: Wellcome Trust

Abstract: Humans have the unique ability to plan and weigh different options before they reach a decision and brain imaging has revealed corresponding anatomical correlates. However, these same brain regions have shown robust patterns of activity independent of any stimuli, an anatomical pattern referred to as the default mode network (DMN). I will explore the behavioural significance of the DMN by testing the hypothesis that endogenous fluctuations reflect the brain's repertoire for future behaviour: mea ning endogenous DMN fluctuations might predict individual planning ability. I will create a large-scale simulation of how temporal patterns of endogenous DMN activity could predict individual planning ability and then test this model with human brain imaging experiments using virtual maze navigation and other planning tasks. Crucially, both simulations and experiments will inform each other throughout my proposed research. These simulations and experiments will demonstrate that decision-making is not only choosing among different stimulus-response options, rather a dynamic process involving the internally driven exploration of learned sequences. My computational approach to brain imaging will provide a mechanistic understanding of how endogenous brain fluctuations relate to decision-making and help us understand how these fluctuations might underlie planning deficits caused by neurodegenerative disease and mental illness.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: A neurocomputational investigation of Pavlovian-instrumental interactions in avoidance.
Funder: Wellcome Trust

Abstract: There are two brain systems that are thought to control action. One system, the model-free (habit) system, is automatic and based on prior experience. The other system, the model-based (goal-directed) system is slower, but more accurate. For example, this system compares alternative routes to obtain valuable outcomes before making an action choice. The first stage of this proposal will characterise how and where the brain arbitrates between these controllers when humans learn to avoid aversive e vents. Secondly, I will investigate how fear interacts with this learning process, by looking at individual differences in, and experimental manipulation of, fear and avoidance learning. I will test if increasing fear causes subjects to rely more on the model-free system when avoiding negative outcomes. Reciprocally, I will test if biasing individuals towards model-free avoidance increases maladaptive retention of acquired fear. Finally, I will use the computational models developed at NYU to te st causal predictions regarding the role of fear, avoidance behaviour and their interplay in patients with generalised anxiety disorder (GAD) and obsessive-compulsive disorder (OCD) diagnoses. In doing so, I hope to formally describe psychiatric dimensions that contribute to many disorders and may be more amenable to pharmacological treatment than categorical psychiatric distinctions.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: How exteroceptive and self-motion cues govern place cell activity and perceived location.
Funder: Wellcome Trust

Abstract: The hippocampus is crucial for spatial navigation, learning and memory. In this brain region, place cells are activated when the animal enters a specific area of the environment. Large numbers of these neurons work together to provide a cognitive map of a familiar environment enabling the animal to navigate and to remember events which occurred in different locations. Place cell responses are shaped by two different sources of information: the location of landmarks in the environment and informa tion derived from the animal's own movement. However, the underlying mechanism by which this information is combined and used to control behaviour is not understood mainly due to the technical limitations. I will overcome these difficulties by using the latest optical imaging combined with genetic techniques to record the activity of large numbers of place cells while the animal is navigating in a virtual world. This will enable me to look at the interaction between the cells, to study the relat ive influences of different types of information and relate each type to the inputs that the hippocampus receives from various other brain regions. Finally, I will use combined behavioural and optical techniques to investigate how perceived location is related to place cell activity.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Understanding the role of mossy cells in the neural dynamics underlying hippocampus-dependent learning and epilepsy.
Funder: Wellcome Trust

Abstract: The general aim of this project is to define the role of mossy cells in hippocampal circuitry and function. Mossy cells are critical components of hippocampal circuitry required for memory formation and learning. In addition, mossy cell pathological loss is a featureof temporal lobe epilepsy (TLE) rodent models. Previous work has shown that mossy cells are absent in adult mice lacking the transcription factor, Prdm8 and PRDM8 mutations have been implicated in patients with learning disabilities and epilepsy. Initially, in vitro electrophysiology in hippocampal slices will enable physiological analysis to be evaluated, with greater detail considering granule cell activity and morphology. This data will provide the bases for entire hippocampal formation recording in vivo as well as, investigation of seizure activity in the absence of mossy cells. Contextual fear discrimination protocols will be adapted to examine the impact of mossy cell loss on pattern separation. Finally, empirical data will be used to build and elaborate two dentate gyrus (DG) based computational models (Scharfmann and Myers. 2009 and Santhakumar et al., 2005), to understand the effect of mossy cell loss on memory performance and seizure activity in relation to underlying hippocampal neural dynamics.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: A viral translating ribosome affinity purification (vir-TRAP) study of changesin gene expression in the hippocampal-prefrontal pathway during memory formation.
Funder: Wellcome Trust

Abstract: Translating ribosome affinity purification (TRAP) is a method of profiling themessenger ribonucleic acids (mRNAs) at the ribosome undergoing protein translation, the end point of gene expression, in a given cell population. Theproject aims to develop a novel viral method of TRAP with increased versatility and precision. This method will be combined with behavioural techniques to profile the changes in gene expression underlying the acquisition of associative recognition memories in hippocampal neurons projecting to the prefrontal cortex. This pathway is also involved in fear learning and spatial working memory and has been called the weak link in psychiatric disorders[1] owing to a lack of research in the area despite its promise for understanding and potentially treating a range of mental illnesses, including schizophrenia and depression. Primary goals of the project are therefore to further our understanding of the mechanisms of memory acquisition at the cellular level and of the potential roles of the hippocampal-prefrontal pathway in disease processes. Furthermore, the experiments will provide a rich dataset of changes in translational expression over time, from which we will build a network of interactions and use mathematical modelling to further our understanding of the dynamics at play.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: A multimodal analysis of retrosplenial function.
Funder: Wellcome Trust

Abstract: First, we will investigate the activity of the retrosplenial cortex (RSC) (andlinked brain areas) in response to sensory stimulation (visual, tactile or both) in normal mice and mice subject to sensory deprivation. We will also explore the effect of pairing stimuli with rewards on a conditioning task and investigate whether familiar and novel objects elicit different responses. Thelevel of activity will be measured by means of optical imaging. Next, we will investigate the impact of RSC lesions on behavioural tasks probing recency memory in rats. The task will be modified to enable optical imaging in mice and further developed to asses the impact of different stimulus properties, temporal order and interference levels. We will also test whether the neurotrophic factor BDNF is required for the formation of RSC-mediated memory by inhibiting BDNF, followed by a set of behavioural tasks in rats. Finally, we will measure the changes in RSC activity following mammilothallamic tract lesions and correlate them with the expression of immediate-early genes (such as c-fos) as well as dendritic spine counts in-vivo in mice.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL