Structural synaptic changes in cortical adaptive plasticity

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• Anthony Holtmaat Département des Neurosciences fondamentales CMU, 1 Rue Michel-Servet 1211 GENEVE 4
• Wednesday 01 April 2009, 09:00-09:45
• Cripps Court, Magdalene College.

If you have a question about this talk, please contact Anna Di Pietro.

To understand the synaptic, cellular and network mechanisms of circuit plasticity in relation to learning and memory, neurons need to be studied in the intact brain over extended periods of time. I will describe a procedure to image neurons and their synapses in the mouse neocortex, using long term high-resolution two-photon laser scanning microscopy through a chronic cranial window, followed by the ultrastructural reconstruction of imaged neurons, using serial section EM. Such studies have shown that proxies for synapses, such as dendritic spines and axonal boutons, are dynamic structures, even in the adult brain. Whereas most spines are persistent for months, a small subset of dendritic spines can appear and disappear over days. The generation and loss of persistent spines in the somatosensory barrel cortex is enhanced after trimming of every other whisker (a paradigm known to induce adaptive functional changes in barrel cortex). Most new persistent spines are added on a subclass of L5B neurons located at the barrel interfaces, where adaptive functional changes are largest. Further evidence for a correlation between functional plasticity and new persistent spine formation is provided by studies in αCaMKII-T286A autophosphorylation mutants. Whisker trimming in these mice fails to induce adaptive receptive field changes and also fails to enhance the addition of new persistent spines. Ultrastructural analysis of new pines and their associated boutons shows that new spines often lack synapses shortly after they appear, whereas spines that persist for more than a few days always have synapses. New synapses are predominantly found on large multisynpase boutons, suggesting that spine growth is followed by synapse formation, preferentially on existing boutons. Altogether these data indicate that novel sensory experience drives the stabilization of new spines and promotes the formation of new synapses on subclasses of cortical neurons. These synaptic changes could underlie experience-dependent functional remodelling of specific neocortical circuits.

This talk is part of the Spring School 2009 - "Regeneration and Plasticity of Neural Circuits" series.

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