Novel tools including high-resolution in vivo functional and structural imaging of neurons, synapses and astrocytes, along with new probes, are transforming the analysis of cortical networks. Such approaches reveal not only how visual cortex networks integrate simple inputs to make complex outputs, but also the mechanisms by which cortical synapses mediate remarkable activity-dependent plasticity during development and in adulthood. The generation of orientation selectivity and of eye-specific connections from the two eyes to visual cortex neurons provides highly sensitive probes of synaptic and network development and function. Brief closure of one eye, for a few hours, during a sensitive period of development causes rapid changes in the strength of drive from not only the closed eye but also from the open eye to cortical neurons, as revealed by repeated imaging of functional drive to the same cells. Repeated imaging in vivo of synapses at precisely identified zones shows that such functional changes are accompanied by specific structural changes at spines, including the loss and gain of spines related to the two eyes and changes in their dynamics and motility. Activity-dependent signaling molecules such as Arc are suspected to have a role in synaptic and network plasticity. By generating Arc-GFP knock-in mice and in vivo imaging of cells that specifically develop without Arc, we have shown that Arc is critical for the selective removal of AMPA receptors and thus for shaping both orientation tuning and the strength of inputs from the two eyes during development. Novel FRET probes of CaMKIIa activation show unexpected mechanisms of synaptic plasticity involving both feedforward Hebbian changes as well as feedback homeostatic changes on short time scales. A major puzzle in cortical physiology concerns the role of astrocytes, which constitute a large fraction of cells of the cerebral cortex. High resolution functional imaging of responses from identified cells utilizing specific astrocyte markers reveals that astrocytes have sharp tuning to visual stimulus features, with responses that are precisely matched to those of adjacent neurons. Signaling between astrocytes and neurons shapes synaptic structure and function, including the magnitude and duration of neuronal responses, and thus influences neuronal computations such as those underlying orientation tuning and the regulation of contrast gain. In addition, astrocytes exquisitely regulate local blood flow into cortex, providing the basis for functional brain imaging signals.
University College Dublin (2009) Proc Physiol Soc 15, SA7
Research Symposium: Plasticity and dynamics of neuron and astrocyte networks in visual cortex
M. Sur1
1. Department of Brain and Cognitive Sciences and Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
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Where applicable, experiments conform with Society ethical requirements.