Research team

Bio-Imaging lab

Expertise

Multimodal application of neuroimaging in combination with electrophysiology, optical imaging and neuromodulation via optogenetics/chemogenetics to understand brain function

Upgrade of 9.4T Bruker BioSpec MRI imaging system to Avance NEO hardware architecture. 01/05/2020 - 30/04/2024

Abstract

Upgrade of the hardware of existing equipment (9.4T MRI system from Bruker) to perform state of the art MRI investigations in the brain of small animals such as mice, rats and birds. This hardware upgrade will enable implementation of all new Bruker software packages.

Researcher(s)

Research team(s)

How the interplay between basal forebrain neuronal populations determines brain state and how this is changed in Alzheimer's disease. 01/10/2018 - 30/09/2022

Abstract

During the last decades, the achievement of a better and improved quality of life has resulted in increased life expectancy. This is mainly due to progress in translational research and development of new therapeutic approaches. The downside is that age is one of the major risk factors for dementias and neurodegenerative disorders such as Alzheimer's disease (AD), characterized by a marked decline of cognitive functions (e.g. short- and long-term memory loss) and dysregulation of higher cortical functions (e.g. impaired judgement and thinking). The pathological condition of these diseases is disabling enough to compromise the activity of everyday life. Lengthening the life span has little value if the quality of life cannot be ensured. Unfortunately, the pathogenesis of AD is still far from being understood and this could be the reason why none of the currently available pharmacological therapies for this disease are satisfactory. Current treatments are purely symptomatic and do not act on the onset and progression of the pathology. It is well known that Basal Forebrain (BF) cholinergic neurons are prone to degeneration during aging as well as in dementias like AD. Furthermore, "the cholinergic hypothesis of geriatric cognitive dysfunction" is also supported by the significant correlation between the level of cholinergic depletion and the degree of cognitive deficits. Acetylcholine is a neuromodulator broadly investigated for its role in learning and memory, but it is not the only player in AD. In fact, in the BF, intermingled with cholinergic neurons, there are also two non-cholinergic neuronal types: GABAergic and glutamatergic neurons. It has been discovered that dysfunctions at the level of glutamatergic and GABAergic systems are involved as well in AD. Until recently, neuroscientists have limited the research of AD to the study of a single neuronal type (mainly BF cholinergic neurons), overlooking the possible role of non-cholinergic neuronal populations (GABAergic and glutamatergic). However, it is of the utmost importance to uncover the interaction between BF cholinergic and non-cholinergic neurons to develop novel strategies for the treatment of AD. The proposed research project aims to investigate the interaction between the three distinct BF populations and to elucidate how the BF cholinergic neuronal activity influences the other two BF neuronal types both in healthy and in pathological conditions. To date, it is still far from being understood how the neural state of the cholinergic neurons influences the GABAergic and glutamatergic neurons in the BF and how these, in turn, adjust cholinergic neuromodulation. We suggest to study the activity of BF neuronal populations and their interactions during spontaneous activity and determine the relationship of the activity of these three neuronal populations with whole brain functional connectivity. Then we will target and stimulate the BF cholinergic neurons using optogenetics to understand how it influences network interactions and to identify the optimal conditions of stimulation in an AD animal model that can induce network states as observed during spontaneous activity in healthy animals. To achieve these goals, we propose a methodological approach that is both innovative and multimodal because it combines cutting edge techniques such as fMRI tools, optogenetics and fiber-optic calcium recording. The results of this study will provide an increased and better understanding of BF neural circuitry, thus opening new future perspectives for the treatment of cognitive disorders.

Researcher(s)

Research team(s)

Does melanopsin mediate seasonal neuroplasticity in starlings ? 01/10/2018 - 30/09/2021

Abstract

Light is an important environmental factor driving many functions in animal physiology. There are two systems for detecting light in animals i) The classical visual system for image formation (IF) and ii) The Non-image-forming (NIF) visual circuit. NIF in mammals is mediated by melanopsin containing intrinsically photoreceptive retinal ganglionic cells and innervates brain regions regulating sleep, circadian functions, cognition etc. We hypothesize that the NIF circuit mediates the light's influence in neuroplasticity of seasonal songbirds. To test this, we use European starling's which shows extensive neuroplasticity in response to seasons, in vivo MRI and molecular biology techniques.

Researcher(s)

Research team(s)

Cholinergic and noradrenergic modulation of memory and mood. 01/10/2018 - 30/09/2021

Abstract

The current therapies of Alzheimer's disease (AD) are insufficient and novel treatments are necessary. Cholinergic and noradrenergic neurotransmitter systems are involved in memory and mood modulation. An add-on effect of increased noradrenergic signalling in addition to the standard therapy of increased cholinergic signalling has been proposed for AD patients. However, the interaction between the two systems is not well understood. In this proposal, we will evaluate the effects of activating via DREADDs 1) cholinergic neurons in medial septum, which project to hippocampus, 2) noradrenergic neurons in locus coeruleus, which project to medial septum and hippocampus, and 3) cholinergic and noradrenergic neurons. We will evaluate the effect of these different modulations on behaviour (memory and mood) and different brain network properties in a promising AD rat model and in healthy rats. We will look at functional connectivity in the brain, oscillations in local field potentials in hippocampus (which reflect local hippocampal network properties), and whole-brain activity state related to sharp-wave ripples, a neuronal event that occurs within hippocampus and that is associated with memory. Finally, we will assess whether early deficits in functional connectivity and cerebral blood flow can predict long-term behavioural outcome in (untreated) AD rats and whether deficits in these parameters can predict the responsiveness to the treatment (one of the three possible modulations).

Researcher(s)

Research team(s)

Multimodal Imaging of cholinergic neuromodulation during specific memory phases in the rodent brain. 01/01/2017 - 31/12/2020

Abstract

Advances in translational research and widespread distribution of therapeutic means have led to dramatic increases in global life expectancy over the past decades. However, at the same time longevity imposes a great impact on the quality of life of the ageing population. Numerous neurological diseases such as various types of dementia (e.g. Alzheimer's) rise exponentially with age inflicting great economic and social burden to the societies. To this end, basic brain research continues to be a major component in providing the necessary insights for the reversal of these trends. Memory and learning are inextricably related to most dementias but our understanding of the underlying mechanisms remains rudimentary. Further, the amount of certain brain chemicals (neurotransmitters), in particular one called acetylcholine, is also reduced. This project will use a combination of state-of-the-art magnetic resonance and calcium imaging in order to a) uncover the relationship between learning and specific pathways of cholinergic transmission by using DREADDs (specifically designed receptors that can be introduced in specific cells and modulate their activity), b) understand the dynamics of this relationship during ageing, and c) test if application of this approach in rodent models of Alzheimer's disease that loose cholinergic cells can ameliorate the effects and improve memory. If successful, this project will provide the basis for developing new therapeutic approaches in the future.

Researcher(s)

Research team(s)

The role of non-cholinergic neurons in cholinergic neuromodulation. 01/10/2018 - 31/10/2019

Abstract

During the last decades, the achievement of a better and improved quality of life has resulted in increased life expectancy. This is mainly due to progress in translational research and development of new therapeutic approaches. The downside is that age is one of the major risk factors for dementias and neurodegenerative disorders such as Alzheimer's disease (AD), characterized by a marked decline of cognitive functions (e.g. short- and long-term memory loss) and dysregulation of higher cortical functions (e.g. impaired judgement and thinking). The pathological condition of these diseases is disabling enough to compromise the activity of everyday life. Lengthening the life span has little value if the quality of life cannot be ensured. Unfortunately, the pathogenesis of AD is still far from being understood and this could be the reason why none of the currently available pharmacological therapies for this disease are satisfactory. Current treatments are purely symptomatic and do not act on the onset and progression of the pathology. It is well known that Basal Forebrain (BF) cholinergic neurons are prone to degeneration during aging as well as in dementias like AD. Furthermore, "the cholinergic hypothesis of geriatric cognitive dysfunction" is also supported by the significant correlation between the level of cholinergic depletion and the degree of cognitive deficits. Acetylcholine is a neuromodulator broadly investigated for its role in learning and memory, but it is not the only player in AD. In fact, in the BF, intermingled with cholinergic neurons, there are also two non-cholinergic neuronal types: GABAergic and glutamatergic neurons. It has been discovered that dysfunctions at the level of glutamatergic and GABAergic systems are involved as well in AD. Until recently, neuroscientists have limited the research of AD to the study of a single neuronal type (mainly BF cholinergic neurons), overlooking the possible role of non-cholinergic neuronal populations (GABAergic and glutamatergic). However, it is of the utmost importance to uncover the interaction between BF cholinergic and non-cholinergic neurons to develop novel strategies for the treatment of AD. The proposed research project aims to investigate the interaction between the three distinct BF populations and to elucidate how the BF cholinergic neuronal activity influences the other two BF neuronal types both in healthy and in pathological conditions. To date, it is still far from being understood how the neural state of the cholinergic neurons influences the GABAergic and glutamatergic neurons in the BF and how these, in turn, adjust cholinergic neuromodulation. We suggest to study the activity of BF neuronal populations and their interactions during spontaneous activity and determine the relationship of the activity of these three neuronal populations with whole brain functional connectivity. Then we will target and stimulate the BF cholinergic neurons using optogenetics to understand how it influences network interactions and to identify the optimal conditions of stimulation in an AD animal model that can induce network states as observed during spontaneous activity in healthy animals. To achieve these goals, we propose a methodological approach that is both innovative and multimodal because it combines cutting edge techniques such as fMRI tools, optogenetics and fiber-optic calcium recording. The results of this study will provide an increased and better understanding of BF neural circuitry, thus opening new future perspectives for the treatment of cognitive disorders.

Researcher(s)

Research team(s)

Seasonal neuroplasticity of visual and auditory system integration: an in vivo MRI study in starling. 01/10/2016 - 30/09/2019

Abstract

This project onderzoeken we of seizoenale neuroplastische veranderingen in sensorische netwerken van seizoenale zangvogels gepaard gaan met functionle veranderingen die leiden tot gedragswijzigingen die reproductie in de hand werken. Het onderzoek maakt gebruik van multisensory fMRI.

Researcher(s)

Research team(s)

Modular confocal microscopy platform with light sheet illumination. 01/05/2016 - 30/04/2020

Abstract

The application concerns an innovative microscopy platform for visualizing cells, tissue specimen and living small model organisms in three dimensions at unprecedented speed and with excellent resolution and contrast. As a unique feature, the platform is equipped with a light-sheet module, which is based on an orthogonal configuration of laser-generated, micrometer-thin plane illumination and sensitive one-shot detection. Seamless integration with confocal modalities enables imaging the same sample from the micro- to the mesoscale. The device has a broad application radius in the neurosciences domain inter alia for studying neurodegeneration and -regeneration (e.g. whole brain imaging, optogenetics); but it also has direct utility in various other fields such as cardiovascular research (e.g. plaque formation and stability), plant developmental research (e.g. protein localization during plant growth) and ecotoxicology (e.g. teratogenicity and developmental defects in zebrafish). Furthermore, its modular construction will enable adaptation and targeted expansion for future imaging needs.

Researcher(s)

Research team(s)

Ultrafast Functional Ultrasound (fUS) Imaging for highly resolved targetted mapping of functional connectivity in the awake mouse brain (FUSIMICE). 01/12/2015 - 30/11/2018

Abstract

In this project, a new imaging methodology (functional Ultra Sound) is developed, tested and compared with resting state functional Magnetic Resonance Imaging to study the functional connectivity between different brain circuits.

Researcher(s)

Research team(s)

Spatial neglect in rodents: a model for studying neuroplasticity at the network level. 01/10/2015 - 30/09/2019

Abstract

Diseases that afflict the brain, such as stroke, are associated with high morbidity for patients and their families and incur a tremendous burden to individuals and the society. Spatial neglect is a frequent consequence of brain damage, manifesting attentional deficits in perceiving and responding to stimuli in the contralesional field. Neglect affects roughly one third of stroke victims and greatly interferes with all daily activities, being one of the most disabling neurological syndromes. Despite partial recovery in the first months after stroke, yet poorly understood, one third of these patients remain severely disabled and require specific treatment. Although a number of treatments exist for human patients none is extremely successful, as we do not understand sufficiently the neural mechanisms underlying the disorder with multiple questions remaining to be addressed. To tackle some of these complicated issues, we propose to use a multimodal approach that combines functional magnetic resonance imaging, electrophysiology and stimulation of neuromodulatory nuclei in a rat model of spatial neglect. These state-of-the-art techniques will be applied after temporary and chronic focal lesions of central nodes of the neglect network in rats causing neglect like deficits that simulate the disorder in humans. Our proposal will significantly advance the understanding of the neural processes involved in neglect and specifically the role of functional connectivity at the neural circuit level. Furthermore, we will evaluate a novel and highly promising rehabilitation method that utilizes the role of neuromodulation in attentional processes by optogenetic stimulation of the cholinergic nucleus basalis of Meynert. If successful, this would provide a tremendous impact both in basic and clinical research and provide the basis for novel rehabilitative approaches in humans (e.g. by deep brain stimulation).

Researcher(s)

Research team(s)

Processes of integration in multi-stable visual motion perception. 15/07/2015 - 14/07/2016

Abstract

Perceptual multi-stability is established when the brain fails to reach a single interpretation of the input from the external world. In the visual modality, a number of ambiguous visual patterns have been described such as the Necker cube, motion plaids, and binocular rivalry. Multi-stable stimuli can provide unique insights into visual processing, as changes in perception are decoupled from changes in the stimulus. Understanding of how multi-stable perception occurs might help one to understand visual perception in general. In order to explore this question, we developed a novel pseudo-plaid stimulus composed of numerous small apertures simulating neural receptive fields. Importantly, this stimulus allows parametric manipulation of the underlying features driving perception and can help us understand the nature of motion integration processes. In this project, we have already used this stimulus in psychophysics experiments with human subjects. Currently the same stimulus is being used in electrophysiological measurements from non-human primate visual cortex. Our findings suggest that stimulus intersections can strongly bias motion perception towards a coherent integrated pattern. Preliminary results from early visual stages (area V1) demonstrate that neurons respond irrespective of perception based on the local stimulus features. On the contrary, neurons at higher visual stages (area MT) modulate their activities in parallel with perception (consistent with human psychophysics) indicating that integration of contextual motion information has taken place.

Researcher(s)

Research team(s)

A system for simultaneous acquisition of MRI and intracranial electrophysiology: a ground-breaking multimodal approach to study brain networks and their components. 01/06/2015 - 31/12/2017

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

Research team(s)

In vivo MR imaging of small laboratory animals. 01/01/2015 - 31/12/2019

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

Research team(s)