Date of Award

4-2012

Embargo Period

10-23-2012

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Sciences

Advisor(s)

Alison Barth

Abstract

Experience-dependent plasticity is the adaptability of brain circuits as a result of changes in neural activity, a phenomenon that has been proposed as the neural basis for important brain function in health and disease. The underlying mechanisms of experience-dependent plasticity can take different forms, depending on the organisms and brain areas under investigation. A better understanding of these mechanisms will help to interpret normal brain function as well as to guide therapies for neurological diseases. Mouse vibrissa system offers great experimental advantages to studying experience-dependent plasticity and the underlying molecular mechanisms at different levels.

Using sensory experience paradigms of unbalanced whisker activity, we find that sensory experience induces rapid synaptic strengthening at excitatory synapses converged onto single layer 2/3 pyramidal neurons, although the plasticity at these synapses displays remarkable input specificity. Furthermore, we discover that recently potentiated layer 4-2/3 excitatory synapses are labile and subject to activity-dependent weakening in vitro. Calcium-permeable AMPARs (CP-AMPARs) that are sometimes associated with synaptic strengthening are not essential for activity-induced synaptic weakening. Finally, we demonstrate that ongoing sensory experience triggers distinct phases of synaptic plasticity, which are tightly correlated with changes in NMDAR properties and function. Taken together, the results from this thesis show distinct manifestations and mechanisms of how sensory experience modulates synaptic properties and neuronal function that may provide insights into information processing and coding in the neocortex.

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