A window into the brain: Imaging neural circuits involved in behaviour and neuropathologies
Lead Research Organisation:
University of Sussex
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
How does the brain processes stimuli to coordinate behavioural processes? Mechanistic
answers to this question will require real-time observations of the activity patterns of neurons
within key circuits of the brain. This level of analysis will also reveal how brain function becomes
compromised as a consequence of drugs, neurodegeneration or inflammation. Optical methods
such as multiphoton microscopy now provide the resolution required to image neuronal and
synaptic activity in awake animals and we will develop these methods to drive the circuit-level
analysis of behaviours such as addiction and neuropathologies such as Alzheimer’s Disease.
We will achieve this by:
1. Developing new methods that allow the imaging and manipulation of neural activity in deep
brain structures of awake animals carrying out cognitive and behavioural tasks. These
approaches will build on our current expertise in multiphoton microscopy and behavioural and
circuits-level neuroscience to provide a ‘window into the brain’.
2. Driving collaboration between molecular neuroscientists who develop new reporter
proteins, sensory and behavioural neuroscientists who implement novel behavioural assays in
which imaging data can be collected and computational neuroscientists who develop software
tools to analyse the resulting large datasets.
3. Initiating ambitious new lines of research that seek to understand the neural circuits
involved in addiction, the recognition of specific stimulus sequences, the cognitive deficits in
Alzheimer’s Disease or the mechanisms of neurovascular coupling in the brain.
Our ambition is to make Sussex a world-leading centre for the circuit-level analysis of sensory
processing and behaviour in vertebrates such as mice and zebrafish. An MRC Discovery Award
will build on our recent investments in multiphoton imaging by allowing us to develop our
technical platform to image subcortical brain structures. This will be a crucial step in expanding
the use of high-resolution imaging methods beyond sensory neuroscientists investigating the
cortex to behavioural neuroscientists studying deeper brain structures. The dissemination of this
expertise within the UK will play a key role in driving research that aims to understand how
neural circuits operate to control behaviour in both healthy and diseased states.
answers to this question will require real-time observations of the activity patterns of neurons
within key circuits of the brain. This level of analysis will also reveal how brain function becomes
compromised as a consequence of drugs, neurodegeneration or inflammation. Optical methods
such as multiphoton microscopy now provide the resolution required to image neuronal and
synaptic activity in awake animals and we will develop these methods to drive the circuit-level
analysis of behaviours such as addiction and neuropathologies such as Alzheimer’s Disease.
We will achieve this by:
1. Developing new methods that allow the imaging and manipulation of neural activity in deep
brain structures of awake animals carrying out cognitive and behavioural tasks. These
approaches will build on our current expertise in multiphoton microscopy and behavioural and
circuits-level neuroscience to provide a ‘window into the brain’.
2. Driving collaboration between molecular neuroscientists who develop new reporter
proteins, sensory and behavioural neuroscientists who implement novel behavioural assays in
which imaging data can be collected and computational neuroscientists who develop software
tools to analyse the resulting large datasets.
3. Initiating ambitious new lines of research that seek to understand the neural circuits
involved in addiction, the recognition of specific stimulus sequences, the cognitive deficits in
Alzheimer’s Disease or the mechanisms of neurovascular coupling in the brain.
Our ambition is to make Sussex a world-leading centre for the circuit-level analysis of sensory
processing and behaviour in vertebrates such as mice and zebrafish. An MRC Discovery Award
will build on our recent investments in multiphoton imaging by allowing us to develop our
technical platform to image subcortical brain structures. This will be a crucial step in expanding
the use of high-resolution imaging methods beyond sensory neuroscientists investigating the
cortex to behavioural neuroscientists studying deeper brain structures. The dissemination of this
expertise within the UK will play a key role in driving research that aims to understand how
neural circuits operate to control behaviour in both healthy and diseased states.
Organisations
People |
ORCID iD |
Publications
Baden T
(2018)
Spikeling: A low-cost hardware implementation of a spiking neuron for neuroscience teaching and outreach.
in PLoS biology
Baden T
(2020)
Understanding the retinal basis of vision across species.
in Nature reviews. Neuroscience
Franke K
(2019)
An arbitrary-spectrum spatial visual stimulator for vision research.
in eLife
Janiak FK
(2022)
Non-telecentric two-photon microscopy for 3D random access mesoscale imaging.
in Nature communications
Maina MB
(2021)
Two decades of neuroscience publication trends in Africa.
in Nature communications
Nevala NE
(2019)
A low-cost hyperspectral scanner for natural imaging and the study of animal colour vision above and under water.
in Scientific reports
Shaw K
(2021)
Neurovascular coupling and oxygenation are decreased in hippocampus compared to neocortex because of microvascular differences.
in Nature communications
Steele O
(2022)
A multi-hit hypothesis for an APOE4 -dependent pathophysiological state
in European Journal of Neuroscience
Yoshimatsu T
(2020)
Fovea-like Photoreceptor Specializations Underlie Single UV Cone Driven Prey-Capture Behavior in Zebrafish.
in Neuron
Zhou M
(2020)
Zebrafish Retinal Ganglion Cells Asymmetrically Encode Spectral and Temporal Information across Visual Space.
in Current biology : CB
| Title | Data from: Zebrafish retinal ganglion cells asymmetrically encode spectral and temporal information across visual space |
| Description | In vertebrate vision, the tetrachromatic larval zebrafish permits non-invasive monitoring and manipulating of neural activity across the nervous system in vivo during ongoing behaviour. However, despite a perhaps unparalleled understanding of links between zebrafish brain circuits and visual behaviours, comparatively little is known about what their eyes send to the brain via retinal ganglion cells (RGCs). Major gaps in knowledge include any information on spectral coding, and information on potentially critical variations in RGC properties across the retinal surface corresponding with asymmetries in the statistics of natural visual space and behavioural demands. Here, we use in vivo two photon (2P) imaging during hyperspectral visual stimulation as well as photolabeling of RGCs to provide a functional and anatomical census of RGCs in larval zebrafish. We find that RGCs' functional and structural properties differ across the eye and include a notable population of UV-responsive On-sustained RGCs that are only found in the acute zone, likely to support visual prey capture of UV-bright zooplankton. Next, approximately half of RGCs display diverse forms of colour opponency including many that are driven by a pervasive and slow blue-Off system - far in excess of what would be required to satisfy traditional models of colour vision. In addition, most information on spectral contrast was intermixed with temporal information. Taken together, our results suggest that zebrafish RGCs send a diverse and highly regionalised time-colour code to the brain. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| URL | http://datadryad.org/stash/dataset/doi:10.5061/dryad.7sqv9s4pm |
| Title | Fovea-like photoreceptor specialisations underlie single UV-cone driven prey capture behaviour in zebrafish |
| Description | In the eye, the function of same-type photoreceptors must be regionally adjusted to process a highly asymmetrical natural visual world. Here we show that UV-cones in the larval zebrafish area temporalis are specifically tuned for UV-bright prey capture in their upper frontal visual field, which uses the signal from a single cone at a time. For this, UV-detection efficiency is regionally boosted 42-fold. Next, in vivo 2-photon imaging, transcriptomics and computational modelling reveal that these cones use an elevated baseline of synaptic calcium to facilitate the encoding of bright objects, which in turn results from expressional tuning of phototransduction genes. Finally, this signal is further accentuated at the level of glutamate release driving retinal networks. These regional differences tally with variations between peripheral and foveal cones in primates and hint at a common mechanistic origin. Together, our results highlight a rich mechanistic toolkit for the tuning of neurons. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| URL | http://datadryad.org/stash/dataset/doi:10.5061/dryad.w0vt4b8n3 |
| Title | Supporting Data for Gradual Not Sudden Change: Multiple Sites of Functional Transition Across the Microvascular Bed |
| Description | The data provided was used to generate the figures in Shaw et al (2022); Gradual Not Sudden Change: Multiple Sites of Functional Transition Across the Microvascular Bed, Frontiers in Aging Neuroscience. Full details of how the data was generated and processed is provided in that paper. The ReadMe file attached to this record gives details on the data including measurements and column headings.A single Excel spreadsheet containing all the data points used for graphs in Figures 4-9 and Supplementary Figures 3-6 as individual work sheets (uploaded as .xlsx), and individual .csv files containing all the data points used for graphs in Figures 4-9 and Supplementary Figures 2-6 (for non-proprietary format). Abstract In understanding the role of the neurovascular unit as both a biomarker and target for disease interventions, it is vital to appreciate how the function of different components of this unit change along the vascular tree. The cells of the neurovascular unit together perform an array of vital functions, protecting the brain from circulating toxins and infection, while providing nutrients and clearing away waste products. To do so, the brain's microvasculature dilates to direct energy substrates to active neurons, regulates access to circulating immune cells, and promotes angiogenesis in response to decreased blood supply, as well as pulsating to help clear waste products and maintain the oxygen supply. Different parts of the cerebrovascular tree contribute differently to various aspects of these functions, and previously, it has been assumed that there are discrete types of vessel along the vascular network that mediate different functions. Another option, however, is that the multiple transitions in function that occur across the vascular network do so at many locations, such that vascular function changes gradually, rather than in sharp steps between clearly distinct vessel types. Here, by reference to new data as well as by reviewing historical and recent literature, we argue that this latter scenario is likely the case and that vascular function gradually changes across the network without clear transition points between arteriole, precapillary arteriole and capillary. This is because classically localised functions are in fact performed by wide swathes of the vasculature, and different functional markers start and stop being expressed at different points along the vascular tree. Furthermore, vascular branch points show alterations in their mural cell morphology that suggest functional specialisations irrespective of their position within the network. Together this work emphasises the need for studies to consider where transitions of different functions occur, and the importance of defining these locations, in order to better understand the vascular network and how to target it to treat disease. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| URL | https://sussex.figshare.com/articles/dataset/Supporting_Data_for_Gradual_Not_Sudden_Change_Multiple_... |
| Title | Supporting Data for Gradual Not Sudden Change: Multiple Sites of Functional Transition Across the Microvascular Bed |
| Description | The data provided was used to generate the figures in Shaw et al (2022); Gradual Not Sudden Change: Multiple Sites of Functional Transition Across the Microvascular Bed, Frontiers in Aging Neuroscience. Full details of how the data was generated and processed is provided in that paper. The ReadMe file attached to this record gives details on the data including measurements and column headings.A single Excel spreadsheet containing all the data points used for graphs in Figures 4-9 and Supplementary Figures 3-6 as individual work sheets (uploaded as .xlsx), and individual .csv files containing all the data points used for graphs in Figures 4-9 and Supplementary Figures 2-6 (for non-proprietary format). Abstract In understanding the role of the neurovascular unit as both a biomarker and target for disease interventions, it is vital to appreciate how the function of different components of this unit change along the vascular tree. The cells of the neurovascular unit together perform an array of vital functions, protecting the brain from circulating toxins and infection, while providing nutrients and clearing away waste products. To do so, the brain's microvasculature dilates to direct energy substrates to active neurons, regulates access to circulating immune cells, and promotes angiogenesis in response to decreased blood supply, as well as pulsating to help clear waste products and maintain the oxygen supply. Different parts of the cerebrovascular tree contribute differently to various aspects of these functions, and previously, it has been assumed that there are discrete types of vessel along the vascular network that mediate different functions. Another option, however, is that the multiple transitions in function that occur across the vascular network do so at many locations, such that vascular function changes gradually, rather than in sharp steps between clearly distinct vessel types. Here, by reference to new data as well as by reviewing historical and recent literature, we argue that this latter scenario is likely the case and that vascular function gradually changes across the network without clear transition points between arteriole, precapillary arteriole and capillary. This is because classically localised functions are in fact performed by wide swathes of the vasculature, and different functional markers start and stop being expressed at different points along the vascular tree. Furthermore, vascular branch points show alterations in their mural cell morphology that suggest functional specialisations irrespective of their position within the network. Together this work emphasises the need for studies to consider where transitions of different functions occur, and the importance of defining these locations, in order to better understand the vascular network and how to target it to treat disease. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| URL | https://sussex.figshare.com/articles/dataset/Supporting_Data_for_Gradual_Not_Sudden_Change_Multiple_... |