Cambridge Neuroscience Event
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Cambridge Neuroscience Workshop on Connectomics
When8th September 2015
WhereWest Road Concert Hall
This workshop will immediately precede the international Cambridge Neuroscience symposium on Imaging the Nervous System. The aim of the workshop is to foster interactions between investigators in Cambridge, distributed across University Departments and MRC Research Institutes, who reconstruct and analyse the structure and function of neural circuits across spatial scales and organisms, using a variety of imaging and analysis techniques. The workshop will be an opportunity to bring these Cambridge investigators together to discuss and contrast distinct and common aims and challenges of their work. REGISTRATION IS NOW CLOSED AND THERE IS A WAITING LIST. PLEASE CONTACT DERVILA FOR DETAILS.
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Programme at a Glance
14:00-14:20 Ed Bullmore, Department of Psychiatry
14:20-14:40 William Schafer, MRC Laboratory of Molecular Biology
14:40-15:00 Gregory Jefferis, MRC Laboratory of Molecular Biology
15:00-15:20 Liria Masuda-Nakagawa, Department of Genetics
15:50-16:10 Simon Laughlin, Department of Zoology
16:10-16:30 Marco Tripodi, MRC Laboratory of Molecular Biology
16:30-16:50 John Apergis-Schoute, Department of Pharmacology
16:50-17:10 Linda Geerligs, MRC Cognition & Brain Sciences Unit
17:10-19:00 Refreshments and Networking at the pub
Ed Bullmore, Department of Psychiatry
Graph theoretical methods have discovered qualitatively similar organisational properties of the connectome (small-worldness, hubs, modules, etc) over many scales of space and time and in many different kinds of neuroscience data. I will briefly discuss two implications of these observations. Theoretically, is it conceivable that the scale-invariant or fractal organization of the connectome reflects general selection pressures, e.g. Cajalian conservation laws, that should be expected to apply consistently from micro to macro scales of brain networks? Translationally, what are the potential upsides of network scale invariance? For example, could fractal conservation of disease- or drug-related effects on network configuration at micro and macro scales make it any easier to build mechanistic and comprehensive accounts of human brain network disorganisation and its treatment in neurodegenerative and mental health disorders?
The multilayer connectome of C. elegans
William Schafer, MRC Laboratory of Molecular Biology
Most connectomics research has focused on mapping synaptic connections between identified neurons. However, in addition to chemical synapses--wired unidirectional connections involving chemical neurotransmission--all brains contain other types of neuronal links with distinct properties acting on different timescales. For example, gap junctions form wired, bidirectional fast electrical connections, whereas monoamine and neuropeptide signaling creates wireless, slow unidirectional connections. We have used published and newly-generated gene expression data to generate a monoamine extrasynaptic connectome for the nematode C. elegans and to characterise its network properties. In combination with existing synaptic and gap junction connectome data, this provides the first opportunity to analyse the structural and functional properties of a multilayer neuronal connectome.
Computational tools for single cell neuroanatomy
Greg Jefferis, MRC Laboratory of Molecular Biology
I will describe some of the computational tools that we have been developing for quantitative single cell neuroanatomy, showcasing some applications in the fly brain, but also examples of datasets from both vertebrate and invertebrate model organisms. We are starting to use these tools in the context of synaptic resolution connectomics, working with reconstructions of electron microscopy data of the complete larval Drosophila nervous system. Our initial experience suggests that they are likely to have significant utility in this area.
A connectomic approach to circuit mechanisms for sensory discrimination
Liria Masuda-Nakagawa, Department of Genetics
Insect mushroom bodies (MBs) are higher brain centers essential for associative olfactory learning, evolutionarily homologous to equivalent mammalian brain regions. The architecture of their input region (calyx), is discernible in the Drosophila larva: Kenyon cell (KC) dendrites appear to encode sensory information by a combinatorial mechanism that integrates relatively few input channels, but can discriminate a large number of odors.
To understand how discrimination is regulated, we aim to identify all neuronal classes innervating the calyx. One neuron mediates a negative feedback loop from MB output. A second class comprises octopaminergic inputs, resembling mammalian adrenergic forebrain innervation from the locus coeruleus; a third class comprises at neurons that must sample activity throughout the calyx. Using GRASP, imaging, EM, and receptor mapping, our goal is a complete description of the circuit logic that regulates the selectivity of sensory representation, in this simple but capable higher brain.
Matching numbers of synapses to input signal quality increases efficiency
Simon Laughlin, Department of Zoology
A fly's first optic neuropile, the lamina, offers unparalleled opportunities to investigate the efficiency with which synapses transfer information. Well-known connectomes show that a large blowfly photoreceptor makes 220 output synapses while the smaller fruitfly photoreceptor makes 40. Using published measurements of SNR's and information rates, I demonstrate that these numbers of synapses match the signal qualities of their respective photoreceptors and I calculate that this matching makes large savings in space, materials and energy. I suggest that these efficiency gains provide good reasons to establish high and low precision parallel pathways, carrying information at different rates.
Neural circuits for goal-oriented actions
Marco Tripodi, MRC Laboratory of Molecular Biology
With the present project we aim to extend our understanding of the circuit logic, neural coding and genetics of networks governing goal-oriented movements by focusing on targeted head movements in mice. Moving from in vitro preparations to in vivo recordings we began to dissect intrinsic properties, circuit design and genetics of neurons involved in the control of spatially tuned movements.
Our study indicates that spatially coherent motor units are anatomically clustered in genetically defined "spatial-motor modules". A paradoxical outcome of such modular nature is that the seemingly continuous motor space would be internally represented, at least at this stage of encoding, by discrete genetically and anatomically defined modules.
The fast and slow of synaptic transmission: Mapping out the functional connectivity of neurochemically-distinct microcircuits
John Apergis-Schoute, Department of Pharmacology
The functional impact of neuromodulator brain systems has historically been probed using pharmacological agents that target the receptors through which they act. These slow-acting neuromodulator systems operate diffusely throughout the nervous system controlling the excitability of target neuronal populations. It is becoming evident that neurons that synthesise and release slow-acting neuromodulators also synthesise and communicate via the relatively fast neurotransmitters glutamate and GABA. The combined postsynaptic impact however of both fast and slow neurotransmission arising from the same neuronal population is poorly understood. Moreover, it is unclear under what cellular conditions endogenous neuromodulators are released. The orexin/hypocretin system is known to play an important role in maintaining wakefulness as disruption in this system results in a narcoleptic phenotype. To demonstrate how the functional connectivity between neurochemically-distinct cellular populations can support biologically-relevant behaviour on the synapse-level, this talk will describe the mechanisms by which endogenously evoked orexin/hypocretin interacts with fast synaptic transmission from the same orexin/hypocretin population for maintaining wakefulness through excitation as well as inhibition of wake-sleep systems.
Functional networks in the human aging brain
Linda Geerligs, MRC Cognition & Brain Sciences Unit
In human neuroimaging, functional connectivity is often used to study the coupling between brain regions over time. Graph theoretical methods can be used to group these brain regions into functional networks of regions that tend to show high connectivity to each other and less connectivity to other regions. The brain regions making up these networks tend to be involved in similar (cognitive) tasks. This division of processes into separate brain networks is thought to optimize the processing efficiency, while requiring minimal amounts of energy. As people age, this functional network architecture becomes less efficient. While connections within networks tend to be reduced with age, connections between networks increase, resulting in decreased segregation between networks in older adults. This loss of network segregation with age is related to a reduction in fluid intelligence.
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