Research: Imaging of synaptic structure and function in the visual system.
My lab uses advanced imaging techniques to study the structure and function of single cells in networks in the intact brain. Although a vast literature describes the development and function of neuronal connectivity, most of this work has been carried out in culture and excised or fixed tissue, where dynamic processes are inferred from static images compared across animals. Little is known about the function of subcellular compartments in the computations carried out by neurons in vivo. The goal of our work is to understand structural and functional changes occurring at synapses during plasticity elicited by sensory stimuli.
My specific interests lie in understanding how visual activity shapes the structure and function of connections between neurons in the visual cortex. During the critical period, closure of one eye leads to a shift in the responses of neurons towards the open eye. My labs current work focuses on the structural basis for this rapid ocular dominance plasticity using in vivo two-photon microscopy to elucidate single cell structure deep in the intact brain. Dendritic spines are the postsynaptic structures of most excitatory synapses in the CNS. Interestingly, spine structure is highly dynamic making the precise morphology of the spine a possible candidate for the coding of synaptic strength. By combining structural two-photon imaging with functional intrinsic signal imaging in the ferret and mouse, we can correlate changes in synaptic structure with changes in response properties of the visual cortex. These experiments have shown increased spine motility as well as increased spine and axon terminal turnover following even one day of monocular deprivation. These synaptic changes occur in the absence of changes in gross dendritic or axonal structure, suggesting that fine scale changes in synaptic connectivity underlie rapid ocular dominance plasticity without an overall remodeling of the pre and postsynaptic scaffold.
My lab is also interested in the mechanisms which underlie structural remodeling at synapses. Imaging carried out in reduced preparations such as the acute brain slice allows us to explore the contributions of different pathways to structural plasticity. Our work has shown that both intracellular pathways and the extracellular matrix are involved in the remodeling of the spine during synaptic plasticity.
Selected peer-reviewed recent publications:
Rittenhouse, C., Majewska, A. (2009) "Synaptic mechanisms of activity-dependent remodeling in visual cortex." J. Exp. Neurosci. 2:23-41.
Kelly, E.A., Tremblay, M-E., McCasland, J., Majewska, A. (2010) "Postsynaptic deregulation in GAP-43 HZ mouse barrel cortex." Cerebral Cortex 20(7):1696-707. PMC 2882825
Tremblay, M-E., Lowery, R. L., Majewska, A. (2010) "Experience-dependent interactions between microglia and synapses in the mouse visual cortex in vivo." PLOS Biology 8(11): e1000527. PMC 2970556
Tropea, D.*, Majewska, A.*, Garcia, R., Sur., M. (2010) "Structural dynamics of synapses in vivo correlate with functional changes during experience-dependent plasticity in visual cortex" J Neuroscience 30: 11086-95. *equal contribution PMC 2932955
Bogart, L., Levy, A., Gladstone, M., Allen P.D., Zettel, M., Ison, J.R., Luebke, A., Majewska, A. (2011) "Loss of prestin does not alter the development of auditory cortical dendritic spines" Neural Plasticity. Vol. 2011 Article ID 305621
Jeong, J.K., Tremere, L.A., Burrows, K., Majewska, A.K., Pinaud, R. (2011) The primary visual cortex is a site of production and sensitivity to estrogens. Plos One. 6(5):e20400. PMC 3101258
Tremblay, M.E., Majewska, A. (2011) "A role for microglia in synaptic plasticity?" Communicative and Integrative Biology 4(2). PMC 3104585