In studies of neural plasticity, one of the outstanding challenges is to connect our growing understanding of cellular and synaptic mechanisms to their consequences for plasticity of whole neuronal circuits. A promising approach is to use optical microscopy to observe the changes in activity that accompany learning;however, conventional methods like multiphoton microscopy cannot monitor neuronal events over large regions at high speeds. A new technique, Objective-Coupled Planar Illumination (OCPI) microscopy, promises orders-of- magnitude increases in the sensitivity and speed of optical physiology. This proposal focuses on extending the spatiotemporal resolution of OCPI microscopy to observe neuronal activity and plasticity at subcellular resolution in thousands of neurons simultaneously.
The mechanisms of learning are among the great unsolved mysteries of the brain, and memory deficits are a major medical problem. To better understand the neuronal basis of learning, we will develop new instruments for observing the changes in the brain during memory formation.
|Xu, Pei Sabrina; Lee, Donghoon; Holy, Timothy E (2016) Experience-Dependent Plasticity Drives Individual Differences in Pheromone-Sensing Neurons. Neuron 91:878-92|
|Liang, Xitong; Holy, Timothy E; Taghert, Paul H (2016) Synchronous Drosophila circadian pacemakers display nonsynchronous CaÂ²âº rhythms in vivo. Science 351:976-81|
|Fu, Xiaoyan; Yan, Yuetian; Xu, Pei S et al. (2015) A Molecular Code for Identity in the Vomeronasal System. Cell 163:313-23|
|Hammen, Gary F; Turaga, Diwakar; Holy, Timothy E et al. (2014) Functional organization of glomerular maps in the mouse accessory olfactory bulb. Nat Neurosci 17:953-61|
|Xu, Pei Sabrina; Holy, Timothy E (2013) Whole-mount imaging of responses in mouse vomeronasal neurons. Methods Mol Biol 1068:201-10|
|Tolokh, Illya I; Fu, Xiaoyan; Holy, Timothy E (2013) Reliable sex and strain discrimination in the mouse vomeronasal organ and accessory olfactory bulb. J Neurosci 33:13903-13|
|Turaga, Diwakar; Holy, Timothy E (2012) Organization of vomeronasal sensory coding revealed by fast volumetric calcium imaging. J Neurosci 32:1612-21|
|Turaga, Diwakar; Holy, Timothy E (2010) Image-based calibration of a deformable mirror in wide-field microscopy. Appl Opt 49:2030-40|