Publications
74 results found
Zhilun Y, Qian W, Ge G, et al., 2014, A Semi-automated Program for Axonal Reconstructions from Time-lapse 2-Photon Images, Publisher: Frontiers Media SA
Allegra Mascaro AL, Cesare P, Sacconi L, et al., 2013, In vivo two-photon imaging of climbing fibers plasticity after laser axotomy, Neurophotonics, Microscopy of the Brain, ISSN: 1605-7422
In the adult nervous system, different neuronal classes show different regenerative behavior. Although previous studies demonstrated that olivocerebellar fibers are capable of axonal regeneration in a suitable environment as a response to injury, we have hitherto no details about the real dynamics of fiber regeneration. We set up a model of singularly axotomized climbing fibers (CF) to investigate their reparative properties in the adult central nervous system (CNS) in vivo. Here we describe the approach followed to characterize the reactive plasticity after injury. © 2013 OSA-SPIE.
Canty AJ, Teles-Grilo Ruivo LM, Nesarajah C, et al., 2013, Synaptic elimination and protection after minimal injury depend on cell type and their prelesion structural dynamics in the adult cerebral cortex., J Neurosci, Vol: 33, Pages: 10374-10383
The axonal and synaptic mechanisms underlying dysfunction and repair of the injured CNS are poorly understood. Unresolved issues include to what degree, when, and how the surviving neurons degenerate and the extent of synaptic remodeling both along the severed axon and in the nearby area. One of the main reasons is the lack of tools to study the complex asynchronous and dynamic features of individual lesioned axon responses in the intact brain. To address these issues, we combined two-photon microscopy and laser microsurgery to image the real-time reorganization of cortical circuitry at synaptic resolution for periods of up to 1 year in the brain of living mice. Injured cortical axons were eliminated proximally through a two-phase retraction process, which continued for at least 3 months postlesion and was independent of the presence of scar tissue. Remarkably, axons which later attempt to regenerate in both the mature and juvenile brain retracted less, raising the possibility that targeting retraction may improve the chances of axon regrowth after axotomy. Comparing prelesion and postlesion dynamics on the same axons over several days and weeks revealed that, although synapse formation rates were unaffected, boutons on injured axons were either rapidly and persistently lost, or extremely resistant, depending on cell-type and their prelesion structural dynamics. Our data suggest a lasting deficiency in synaptic output on surviving injured cortical axons and a surprising difference in the vulnerability of synaptic boutons after axotomy, which depend on cell-type and their recent history.
Allegra Mascaro, Cesare, Sacconi, et al., 2013, In vivo single branch axotomy induces GAP-43 dependent sprouting and synaptic remodeling in cerebellar cortex, Proceedings of the National Academy of Sciences of the United States of America
Canty AJ, Huang L, Jackson JS, et al., 2013, <i>In</i>-<i>vivo</i> single neuron axotomy triggers axon regeneration to restore synaptic density in specific cortical circuits, NATURE COMMUNICATIONS, Vol: 4, ISSN: 2041-1723
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- Citations: 107
Grillo FW, Song S, Teles-Grilo Ruivo LM, et al., 2013, Increased axonal bouton dynamics in the aging mouse cortex., Proc Natl Acad Sci U S A, Vol: 110, Pages: E1514-E1523
Aging is a major risk factor for many neurological diseases and is associated with mild cognitive decline. Previous studies suggest that aging is accompanied by reduced synapse number and synaptic plasticity in specific brain regions. However, most studies, to date, used either postmortem or ex vivo preparations and lacked key in vivo evidence. Thus, whether neuronal arbors and synaptic structures remain dynamic in the intact aged brain and whether specific synaptic deficits arise during aging remains unknown. Here we used in vivo two-photon imaging and a unique analysis method to rigorously measure and track the size and location of axonal boutons in aged mice. Unexpectedly, the aged cortex shows circuit-specific increased rates of axonal bouton formation, elimination, and destabilization. Compared with the young adult brain, large (i.e., strong) boutons show 10-fold higher rates of destabilization and 20-fold higher turnover in the aged cortex. Size fluctuations of persistent boutons, believed to encode long-term memories, also are larger in the aged brain, whereas bouton size and density are not affected. Our data uncover a striking and unexpected increase in axonal bouton dynamics in the aged cortex. The increased turnover and destabilization rates of large boutons indicate that learning and memory deficits in the aged brain arise not through an inability to form new synapses but rather through decreased synaptic tenacity. Overall our study suggests that increased synaptic structural dynamics in specific cortical circuits may be a mechanism for age-related cognitive decline.
Bloomfield P, Howes O, De Paola V, 2013, Chronic administration of haloperidol in rats and its effect on microglial cell density and whole brain weight and volume, European Neuropsychopharmacology, Vol: 23, Pages: s20-s21, ISSN: 1873-7862
Allegra-Mascaro AL, Cesare P, Sacconi L, et al., 2013, In vivo reactive neural plasticity investigation by means of correlative two photon : electron microscopy., International Society for Optics and Photonics, San Francisco, USA
Bloomfield P, Howes O, De Paola V, 2013, Cortical Effects of Chronic Haloperidol Administration in rats., ECPN 2013, Nice, France
Allegra Mascaro A, Cesare P, Sacconi L, et al., 2013, In vivo reactive neural plasticity investigation by means of correlative two photon : electron microscopy., Proc. SPIE 8588, Multiphoton Microscopy in the Biomedical Sciences
In the adult nervous system, different populations of neurons correspond to different regenerative behavior. Although previous works showed that olivocerebellar fibers are capable of axonal regeneration in a suitable environment as a response to injury1, we have hitherto no details about the real dynamics of fiber regeneration. We set up a model of singularly axotomized climbing fibers (CF) to investigate their reparative properties in the adult central nervous system (CNS) in vivo. Time lapse two-photon imaging has been combined to laser nanosurgery2, 3 to define a temporal pattern of the degenerative event and to follow the structural rearrangement after injury. To characterize the damage and to elucidate the possible formation of new synaptic contacts on the sprouted branches of the lesioned CF, we combined two-photon in vivo imaging with block face scanning electron microscopy (FIB-SEM). Here we describe the approach followed to characterize the reactive plasticity after injury. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
Canty A, Huang L, Jackson J, et al., 2012, In vivo 2-photon imaging of axonal regeneration and synaptic remodelling after laser-mediated micro lesions in the adult brain., Society for Neuroscience Meeting (selected for oral presentation)
Holtmaat A, de Paola V, Wilbrecht L, et al., 2012, Imaging neocortical neurons through a chronic cranial window., Cold Spring Harb Protoc, Vol: 2012, Pages: 694-701
The rich structural dynamics of axonal arbors and neuronal circuitry can only be revealed through direct and repeated observations of the same neuron(s) over time, preferably in vivo. This protocol describes a long-term, high-resolution method for imaging neocortical neurons in vivo, using a combination of two-photon laser scanning microscopy (2PLSM) and a surgically implanted chronic cranial window. The window is used because the skull of most mammals is too opaque to allow high-resolution imaging of cortical neurons. Using this method, it is feasible to image the smallest neuronal structures in the superficial layers of the neocortex, such as dendritic spines and axonal boutons. Because the surface area of the craniotomy is relatively large, this technique is even suitable for use when labeled neurons are relatively uncommon. The surgery and imaging procedures are illustrated with examples from our studies of structural plasticity in the developing or adult mouse brain. The protocol is optimized for adult mice; we have used mice up to postnatal day 511 (P511). With minor modifications, it is possible to image neurons in rats and mice from P2. Most of our studies have used the Thy1 promoter to drive expression of fluorophores in subsets of cortical neurons.
Cambray S, Arber C, Little G, et al., 2012, Activin induces cortical interneuron identity and differentiation in embryonic stem cell-derived telencephalic neural precursors, NATURE COMMUNICATIONS, Vol: 3, ISSN: 2041-1723
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- Citations: 52
De Paola V, 2012, Zhilun Yang, Qian Wang, Ge Gao, Xuesong Li, Federico Grillo*, Valentina Ferretti*, Vincenzo De Paola* and Sen Song. A Semi-automated Program for Axonal Reconstructions from Time-lapse 2-Photon Images. Neuroinformatics 2012, Munich, Germany
De Paola V, 2012, A. L. Allegra Mascaro*, P. Cesare*, L. Sacconi*, G. Grasselli, V. De Paola, G. W. Knott, P. Strata and F.S. Pavone. Climbing fibers reactive plasticity after laser axotomy. SFN 2012, New Orleans, USA (selected for oral presentation)
De Paola V, 2012, Canty, A.J, Huang, L., Jackson, J., Ruivo, L. Knott, G., Bohumil M., Nesarajan T., Little G., De Paola, V. In vivo 2-photon imaging of axonal regeneration and synaptic remodelling after laser-mediated micro lesions in the adult brain. SFN 2012 New Orleans, USA (selected for oral presentation)
De Paola V, 2012, Grillo, F, Song, S, Teles-Grilo Ruivo, LM, Huang, L, Ge, G, Knott, G, Ferretti, V, Thompson, D, Little, G and De Paola, V. In vivo 2-photon imaging reveals increased axonal bouton dynamics in the aging mouse cortex. SFN 2012, New Orleans, USA
De Paola V, 2012, A. L. Allegra Mascaro*, P. Cesare*, L. Sacconi*, G. Grasselli, V. De Paola, G. W. Knott, P. Strata and F.S. Pavone. Climbing fibers reactive plasticity after laser axotomy. SFN 2012, New Orleans, USA (selected for oral presentation)
De Paola V, 2012, Zhilun Yang, Qian Wang, Ge Gao, Xuesong Li, Federico Grillo*, Valentina Ferretti*, Vincenzo De Paola* and Sen Song. A Semi-automated Program for Axonal Reconstructions from Time-lapse 2-Photon Images. Neuroinformatics 2012, Munich, Germany
Brown KM, Barrionuevo G, Canty AJ, et al., 2011, The DIADEM Data Sets: Representative Light Microscopy Images of Neuronal Morphology to Advance Automation of Digital Reconstructions, NEUROINFORMATICS, Vol: 9, Pages: 143-157, ISSN: 1539-2791
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- Citations: 99
Canty AJ, De Paola V, 2011, Axonal Reconstructions Going Live, NEUROINFORMATICS, Vol: 9, Pages: 129-131, ISSN: 1539-2791
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- Citations: 5
Canty AJ, De Paola V, 2011, Axonal Reconstructions Going Live, Neuroinformatics, Pages: 1-3, ISSN: 1539-2791
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- Citations: 3
Canty A, Huang L, De Paola V, 2010, In vivo 2-photon imaging of laser-mediated microlesions in the adult brain., Australian Neuroscience Annual Meeting, Sydney, AUS (selected for oral presentation)
De Paola, 2010, Canty, AJ and De Paola, V (2010). In vivo 2-photon imaging of laser-mediated microlesions in the adult brain. Australian Neuroscience Annual Meeting, Sydney, AUS – selected for oral presentation
Hugel S, Abegg M, de Paola V, et al., 2009, Dendritic Spine Morphology Determines Membrane-Associated Protein Exchange between Dendritic Shafts and Spine Heads, CEREBRAL CORTEX, Vol: 19, Pages: 697-702, ISSN: 1047-3211
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- Citations: 18
Holtmaat A, Bonhoeffer T, Chow DK, et al., 2009, Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window., Nat Protoc, Vol: 4, Pages: 1128-1144
To understand the cellular and circuit mechanisms of experience-dependent plasticity, neurons and their synapses need to be studied in the intact brain over extended periods of time. Two-photon excitation laser scanning microscopy (2PLSM), together with expression of fluorescent proteins, enables high-resolution imaging of neuronal structure in vivo. In this protocol we describe a chronic cranial window to obtain optical access to the mouse cerebral cortex for long-term imaging. A small bone flap is replaced with a coverglass, which is permanently sealed in place with dental acrylic, providing a clear imaging window with a large field of view (approximately 0.8-12 mm(2)). The surgical procedure can be completed within approximately 1 h. The preparation allows imaging over time periods of months with arbitrary imaging intervals. The large size of the imaging window facilitates imaging of ongoing structural plasticity of small neuronal structures in mice, with low densities of labeled neurons. The entire dendritic and axonal arbor of individual neurons can be reconstructed.
De Paola V, 2009, Imaging synaptic plasticity in the healthy and diseased brain., Mouse Neurological and Behavioural Forum 2
Holtmaat A, De Paolaa V, Wilbrecht L, et al., 2008, Imaging of experience-dependent structural plasticity in the mouse neocortex <i>in vivo</i>, BEHAVIOURAL BRAIN RESEARCH, Vol: 192, Pages: 20-25, ISSN: 0166-4328
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- Citations: 39
Holtmaat, De Paola, Wilbrecht, et al., 2008, Imaging of Experience-Dependent Structural Plasticity in the Mouse Neocortex in vivo, Research and Perspectives in Alzheimer's Disease, Pages: 37-49, ISSN: 0945-6066
The functionality of adult neocortical circuits can be altered by novel experiences or learning. This functional plasticity appears to rely on changes in the strength of neuronal connections that were established during development. Here we will describe studies in which we have addressed whether structural changes, including the remodeling of axons and dendrites with synapse formation and elimination, could underlie experience-dependent plasticity in the adult neocortex.Using 2-photon laser-scanning microscopy transgenic mice expressing GFP in a subset of pyramidal cells, we have observed that a small subset of dendritic spines continuously appear and disappear on a daily basis,whereas themajority of spines persists formonths. Axonal boutons fromdifferent neuronal classes displayed similar behavior, although the extent of remodeling varied. Under baseline conditions, new spines in the barrel cortex were mostly transient and rarely survived for more than a week. However, when every other whisker was trimmed (a paradigm known to induce adaptive functional changes in barrel cortex), the generation and loss of persistent spines was enhanced. Ultrastructural reconstruction of previously imaged spines and boutons using serial section electron microscopy showed that new spines slowly formsynapses. New spines that persisted for a few days always had synapses, whereas very young spines often lacked synapses. New synapses were predominantly found on large, multisynapse boutons, suggesting that spine growth is followed by synapse formation, preferentially on existing boutons.Altogether our data indicate that novel sensory experience drives the stabilization of new spines on subclasses of cortical neurons and promotes the formation of new synapses. These synaptic changes likely underlie experience-dependent functional remodeling of specific neocortical circuits.
holtmaat A, De Paola V, Wilbrecht L, et al., 2008, Imaging of Experience-Dependent Structural Plasticity in the Mouse Neocortex in vivo
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