DNA · Dendritic integration by nanoscale neuroanatomy
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-09-01 → 2018-11-20
- EU contribution
- €173,076
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Dendritic integration by nanoscale neuroanatomy
How single neurons integrate and process incoming synaptic signals to generate a physiologically meaningful output remains a fundamental question in neuroscience. Long standing theoretical work predicts that nanoscale morphology of dendritic spines, the sites of excitatory synapses where the neuronal communication occur, plays a major role in synaptic function and dendritic integration of synaptic inputs. Moreover, brain disorders of neurodevelopment and ageing, which poses a substantial societal burden are increasingly associated with deficits in dendritic spines. My overall goal in the Marie Słodowska-Curie Actions EF project-DNA was to examine how nanoscale dendritic spine morphology directly influences synaptic function and dendritic integration of pyramidal neurons over brain development. This has been a technically challenging question to address: electron microscopy allows the visualisation of spine ultrastructure, but it only provides a static snapshot; although, conventional light microscopy enables live cell imaging, its spatial resolution is diffraction limited. I proposed to use state-of-the-art superresolution technique, STED microscopy that allows live cell imaging with high spatial resolution in combination with physiological methods. I find that the spine morphology and diffusion coupling of spines to the dendrite are dynamically regulated over brain development. In particular there is an age specific transient increase in diffusion coupling of spines coordinated with a widening and shortening of their necks. Together with my neurocomputational collaborator, I am currently developing a computational model based on the morphology data to further investigate how the microphysiology of dendritic spines and the integration of inputs onto multiple spines might be influenced by spine morphology over brain development.
Data: CORDIS, © European Union
Project objective
Understanding how single neurons integrate and process incoming synaptic signals to generate a physiologically meaningful output remains a fundamental question in neuroscience. While much is known about how the integration of synaptic inputs is governed by overall dendritic geometry and ionic conductances along the dendritic membrane, the role of the micro-anatomical structure is yet to be deciphered. Although theoretical work suggests that structural details of dendritic spines might play a major role for synaptic function and dendritic integration, it has been experimentally difficult to address this long-standing hypothesis. While electron microscopy allows the visualisation of spine ultrastructure, it is incompatible with studying spine function in live brain tissue. I propose to combine state-of-the-art STED microscopy with holographic photolysis to examine the influence of spine morphology on dendritic integration of CA1 pyramidal neurons. STED microscopy will reveal spine morphology, while holographic photolysis will be used to stimulate multiple synapses at the same time with high spatio-temporal precision. This novel approach, relying also on electrophysiology and compartmental modelling, will make it possible to study the influence of nanoscale morphology on dendritic integration of multiple synaptic inputs. The project builds on my expertise in cell biology and neuroanatomy, and will give me the opportunity to master advanced opto-physiological methods in a host environment that is well known for bio-imaging and neuroscience. Given my strong background in neurodevelopmental disorders, the project will push the knowledge frontier on neuronal processing and will provide a framework for research into basic mechanisms of neurological disorders.
Original text from CORDIS.
Participants
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union