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Experience-dependent structural plasticity of synapses in vivo

Applicant Holtmaat Anthony
Number 120685
Funding scheme Project funding (Div. I-III)
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.04.2008 - 31.03.2011
Approved amount 360'000.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Cellular Biology, Cytology

Keywords (11)

synaptic plasticity; 2-photon microscopy; dendritic spines; barrel cortex; experience-dependent plasticity; plasticity; imaging; synapses; dendrites; spines; axons

Lay Summary (English)

Lead
Lay summary
When an individual undergoes a novel sensory experience the neurons in the brain that handle this information adapt in order to optimize future processing of the same information and to associate it with other inputs. The functional optimization of neuronal processing has previously been measured using electrodes. This has taught us that, after changes in input, the synaptic connections become stronger between some neurons and weaker between others. Another way to express this is 'that some neurons have changed the loudness with they talk to other neurons'. It was generally believed that the synaptic changes (also called synaptic plasticity) happen in synapses that have long before been established during development of the brain. However, more recently we and others have found that new synapses are continuously formed and lost even in the adult brain, as if neurons are always looking for ways to optimize their connections. The magnitude of these synapse additions and losses is regulated by sensory experience.In the current project we aim to study how sensory input regulates the size and stability of new and old synaptic connections. To do this we use a microscopic technique with which we can peek into the brain of transgenic mice that express a fluorescent marker in particular synapses. This way we can directly monitor the presence and size of synapses. We do this repeatedly over the time course of a month, keeping track of the stable synapses and the ones that appear and disappear. We perform these measurements in a part of the brain that processes information from the whiskers. The sensory input through the whiskers can easily and painlessly be manipulated, so we can compare 'normal' mice with mice that undergo novel sensory experiences. By comparing all these parameters we hope to gain insight in the mechanisms of synaptic plasticity in the intact mouse brain. This is ultimately important for our understanding of learning and memory. New insights from this work will also help to advance the design of new strategies towards memory enhancement and repair in neurological disorders such as Alzheimer's and stroke.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
135631 Long-term potentiation and the modification of synaptic structures in vivo 01.04.2011 Project funding (Div. I-III)
153448 Activity-dependent functional and structural plasticity in the somatosensory cortex in vivo 01.04.2014 Project funding (Div. I-III)
139229 Platform for integrated mouse behavior (PIMB) 01.12.2011 R'EQUIP
127289 Structure, Function and Plasticity of the Barrel Cortex 01.01.2010 Sinergia
153448 Activity-dependent functional and structural plasticity in the somatosensory cortex in vivo 01.04.2014 Project funding (Div. I-III)

Abstract

Novel sensory experience can lead to adaptive changes in the functional properties of the adult neocortex. Such experience-dependent cortical plasticity is thought to be an important aspect of perceptual learning, and to rely on activity-dependent strengthening and weakening of synapses that were established during development. However, an increasing number of studies suggests that ongoing anatomical plasticity, including synapse formation and elimination could be an additional substrate for adult cortical plasticity. However, there is a paucity of information about how anatomical plasticity relates to functional plasticity; which strategies are used and which circuits are involved. Real-time imaging studies have shown that proxies for synapses, such as dendritic spines and axonal boutons, are dynamic structures, and that changes in their size reflect changes in synaptic strength. Imaging studies in the adult mouse somatosensory cortex in vivo have shown that whereas most spines are persistent for months, a small subset of dendritic spines can appear and disappear over days. This growth and retraction of spines can be modulated by changes in experience. Thus, the brain appears to have a number of options available through which to modify its circuits.We hypothesize that cortical plasticity resides in a combination of the strengthening and weakening of pre-existing synaptic connections, and growth and retraction of dendritic spines. These mechanisms specifically operate within those circuits that relay cortical plasticity in the adult cortex. We aim to, (1) characterize the loci of experience-dependent spine and synapse formation, and (2) image experience-dependent synaptic strengthening and weakening of pre-existing synapses, in the adult barrel cortex in vivo.
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