Synaptic Changes During Ocular Dominance Plasticity
- Dr. Brandon Harvey National Institute on Drug Abuse
Figure 1. Imaging dendrites in vivo. Images show a projected stack of apical dendritic tuft of a layer 5 pyramidal cell (top left), a coronal reconstruction of this dendrite (bottom left) and a magnified image of the boxed area showing dendritic spines.
Our group uses advanced imaging techniques to study the structure and function of single cells in networks in the intact brain in order to understand 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 in the visual cortex towards the open eye. Our 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.
Figure 2. Using double stranded adenoassociated virus to label astrocytes (left) and neurons (right) with fluorescent proteins. Green represents GFP expression, red is immunolabel for GFAP, an astrocytic protein.
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 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.
In vivo imaging of layer 5 neurons in a transgenic mouse expressing GFP. Notice that dendritic spines are clearly visible on the apical tuft, while cell bodies and dendrites are visible up to layer 5 (650µm below the level of the pia).
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. Additionally, we are exploring changes in the extracellular matrix elicited by changed in sensory-driven activity, as a possible mechanisms for mediating structural changes at synapses during plasticity. To enhance our imaging experiments we also explore new labeling methodologies that allow the fluorescent tagging of brain elements for in vivo imaging.« back to all projects