Research Groups > Experimental and Clinical Neuroscience Neuroplasticity and Disease

Learning and recovery from brain damage are remarkable examples of neural plasticity. Synaptic elements that mediate most of these adaptive responses are vulnerable targets in a variety of common brain disorders, including Alzheimer's and stroke.

To date, many fundamental questions about synaptic function and plasticity, despite their importance, remain unanswered‚ for example:

  • Are synaptic sites in the adult brain fixed or can learning and memory change them?
  • Which cellular signaling pathways underlie the stabiliy or modification of neuronal connections and how can they be manipulated to design new therapies for neurological diseases?

To address these questions we use a combination of behavioral and advanced molecular genetic, imaging and anatomical techniques. We have recently tracked adult neocortical circuits over several months in vivo using 2-photon microscopy and found cell-type specific dynamics. We are now investigating the molecular mechanisms underlying normal and pathological neuronal network alterations, and the cellular and synaptic basis of learning and of common neuropathologies such as fragile-X syndrome and brain injury. Our primary objective is to discover synaptic and circuit phenotypes at early stages of disease that could be used as therapeutic targets.


Figure 1. Plasticity of adult cortical synapses in vivo on postnatal days (PND) 98-114. Bar, 5 µm (Images taken with a 2-photon microscope.)



Figure 2. Imaging synaptic molecules in vivo. An axon (red) and synaptophysin (green) visualised through a cranial window on postnatal days (PND) 240-310. Bar, 5 µm (Put mouse over image to play animation.)

 Neuroplasticity and Disease
Group head
Vincenzo De Paola
Vincenzo De Paola(Dr) Telephone 35840
v.depaola@csc.mrc.ac.uk
Group members
Peter Bloomfield
Peter Bloomfield(Mr) p.bloomfield11@imperial.ac.uk
Federico Grillo
Federico Grillo(Mr) Telephone 38294
f.grillo09@imperial.ac.uk
Lieven Huang
Lieven Huang(Dr) Telephone 38294
lieven.huang@imperial.ac.uk
Leonor Ruivo Grilo
Leonor Ruivo Grilo(Miss) Telephone 38294
Contact details
Group website:
http://www1.imperial.ac.uk/medicine/people/vincenzo.depaola/

Telephone:
+44 (0) 20 8383 5840 (office)
+44 (0) 20 8383 8250 (administrator)

Facsimile: +44 (0) 20 8383 8306
Selected publications
Canty, A. J., De Paola, V. (2011). Axonal reconstructions going live. Neuroinformatics, in press. Abstract

Holtmaat, A.*, Bonhoeffer, T., Chow, D. K., Chuckowree, J., De Paola, V.*, Hofer, S. B., Hübener, M.*, Keck, T., Knott, G.*, Lee, W. C., Mostany, R., Mrsic-Flogel, T. D., Nedivi, E.*, Portera-Cailliau, C.*, Svoboda, K., Trachtenberg, J. T.*, Wilbrecht, L. (2009). Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window. Nature Protoc. 4(8):1128-44. (* Corr authors) Abstract

De Paola, V., Holtmaat, A., Knott, G., Song, S., Wilbrecht, L., Caroni, P. & Svoboda, K. (2006). Cell type-specific structural plasticity of axonal branches and boutons in the adult neocortex. Neuron 49, 861-875. Abstract | Full text

De Paola, V., Arber, S. & Caroni, P. (2003). AMPA receptors regulate dynamic equilibrium of presynaptic terminals in mature hippocampal networks. Nature Neuroscience 6, 491-500. Abstract

Livet, J., Sigrist, M., Stroebel, S., De Paola, V., Price, S. R., Henderson, C. E., Jessell, T. M. & Arber, S. (2002). ETS gene Pea3 controls the central position and terminal arborization of specific motor neuron pools. Neuron 35, 877-892. Abstract | Full text

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