synaptic plasticity; dendritic spines; barrel cortex; experience-dependent plasticity; 2-photon microscopy; long-term potentiation
Pouchelon Gabrielle, Gambino Frédéric, Bellone Camilla, Telley Ludovic, Vitali Ilaria, Lüscher Christian, Holtmaat Anthony, Jabaudon Denis (2014), Modality-specific thalamocortical inputs instruct the identity of postsynaptic L4 neurons., in Nature
, not known yet(not known ), not known-not known.
Maco Bohumil, Cantoni Marco, Holtmaat Anthony, Kreshuk Anna, Hamprecht Fred A, Knott Graham W (2014), Semiautomated correlative 3D electron microscopy of in vivo-imaged axons and dendrites., in Nature protocols
, 9(6), 1354-66.
Cane Michele, Maco Bohumil, Knott Graham, Holtmaat Anthony (2014), The Relationship between PSD-95 Clustering and Spine Stability In Vivo, in JOURNAL OF NEUROSCIENCE
, 34(6), 2075-2086.
Maco B, Holtmaat A, Cantoni M, Kreshuk A, Straehle CN, Hamprecht FA, Knott GW (2013), Correlative in vivo 2 photon and focused ion beam scanning electron microscopy of cortical neurons., in PLoS One
, 8(2), e57405.
Holtmaat Anthony, Randall Jerome, Cane Michele (2013), Optical imaging of structural and functional synaptic plasticity in vivo, in EUROPEAN JOURNAL OF PHARMACOLOGY
, 719(1-3), 128-136.
Schubert V, Lebrecht D, Holtmaat A (2013), Peripheral deafferentation-driven functional somatosensory map shifts are associated with local, not large-scale dendritic structural plasticity., in J Neurosci
, 33(22), 9474-9487.
Holtmaat Anthony, de Paola Vincenzo, Wilbrecht Linda, Trachtenberg Josh T, Svoboda Karel, Portera-Cailliau Carlos (2012), Imaging Neocortical Neurons through a Chronic Cranial Window., in Helmchen and Konnerth (ed.), Cold Spring Harbor press, Cold Spring Harbor, NY, USA, 1-1.
Gambino Frédéric, Holtmaat Anthony (2012), Spike-timing-dependent potentiation of sensory surround in the somatosensory cortex is facilitated by deprivation-mediated disinhibition, in Neuron
, 75, 490-502.
Gambino Frédéric, Holtmaat Anthony (2012), Synapses let loose for a change: inhibitory synapse pruning throughout experience-dependent cortical plasticity., in Neuron
, 74(2), 214-7.
Novel sensory experience leads to changes in the functional properties of the adult neocortex. Experience-dependent cortical plasticity is thought to be an important aspect of perceptual learning, and likely depends on activity-dependent strengthening and weakening of pre-established synapses as well as on structural plasticity, including synapse formation and elimination. There is a paucity of information on how structural plasticity relates to functional plasticity in vivo. In vitro studies have shown that synaptic structures such as spines undergo rapid modifications upon strong synaptic stimulation, inhibition or LTP and LTD-like processes. However, in vivo studies so far have mostly focused on spine formation and elimination in relation to long-term sensory map plasticity and motor learning. Detailed information on the structural changes of pre-established synapses in vivo, that putatively relate to early phases of neuronal plasticity is currently lacking. We hypothesize that immediate forms of plasticity in vivo include structural changes of pre-established synaptic connections, analogous to the observations in LTP and LTD paradigms in brain slices. In this research proposal we will use an experimental strategy that combines two-photon laser scanning microscopy (2PLSM) with whole-cell electrophysiological recordings in vivo to study spine structural changes during whisker stimulation induced LTP and LTD. We will also perform a detailed analysis of subcellular structural changes in experience-dependent plasticity paradigms in vivo by measuring sizes and the relocation of dendritic organelles such as the PSD, cytoskeleton, ER and mitochondira. Furthermore, in collaboration with G. Knott at the EPFL in Lausanne we will develop and employ a novel method for high throughput correlative reconstruction of the in vivo-imaged dendrites’ ultrastructure, based on focused ion beam milling combined with serial section scanning EM. Improving our knowledge of how neurons in the cortex modulate the structure of their synaptic connections in response to changes in input and experience is key to understanding how we store information and acquire new skills. In addition, it will help to advance the design of new strategies towards memory enhancement and neuronal repair in neurodegenerative diseases and after traumatic injury.