The experiments proposed in this application investigate the roles of dendritic spine growth and retraction in experience-dependent plasticity in the mouse visual cortex. Recent evidence indicate that dendritic spines are dynamic in the developing and adult cortex: new spines appear daily and grow towards axons to establish novel synapses while some existing spines retract, breaking their synaptic connection. These changes in synaptic connectivity may play important roles in rapidly rewiring cortical circuits during experience-dependent plasticity. The extent to which spine growth and retraction underlie functional changes in cortical circuits will be examined in transgenic mice expressing a green fluorescent protein transgene. 2-photon laser scanning microscopy and intrinsic signal optical imaging will used to repeatedly image spine dynamics and functional changes in cortical ocular dominance in vivo over periods of weeks in the same mice before and after monocular deprivation. By imaging changes in structure and function in the same preparation, it will be possible to determine whether synapse elimination underlies the functional loss of deprived eye inputs and novel synapse formation underlies the gradual strengthening of experienced eye inputs. In vivo electrophysiology and fixed tissue anatomy will be used to determine which cells in which layers are the first to alter their responsiveness and connectivity following monocular deprivation and to map the progression of these changes through the remainder of the cortical circuit. Taken together, these experiments should provide a detailed understanding of the onset and progression of experience-dependent changes in cortical structure and function at the level of receptive fields and synapses. Results from these experiments may aid in the provision of rationally-based therapeutic approaches to amblyopia, scotoma, and stroke.
|Kuhlman, Sandra J; Olivas, Nicholas D; Tring, Elaine et al. (2013) A disinhibitory microcircuit initiates critical-period plasticity in the visual cortex. Nature 501:543-6|
|Wyatt, Ryan M; Tring, Elaine; Trachtenberg, Joshua T (2012) Pattern and not magnitude of neural activity determines dendritic spine stability in awake mice. Nat Neurosci 15:949-51|
|Kuhlman, Sandra J; Tring, Elaine; Trachtenberg, Joshua T (2011) Fast-spiking interneurons have an initial orientation bias that is lost with vision. Nat Neurosci 14:1121-3|
|Smith, Spencer L; Trachtenberg, Joshua T (2010) The refinement of ipsilateral eye retinotopic maps is increased by removing the dominant contralateral eye in adult mice. PLoS One 5:e9925|
|Faguet, Joshua; Maranhao, Bruno; Smith, Spencer L et al. (2009) Ipsilateral eye cortical maps are uniquely sensitive to binocular plasticity. J Neurophysiol 101:855-61|
|Matter, Cheryl; Pribadi, Mochtar; Liu, Xin et al. (2009) Delta-catenin is required for the maintenance of neural structure and function in mature cortex in vivo. Neuron 64:320-7|
|Chow, David K; Groszer, Matthias; Pribadi, Mochtar et al. (2009) Laminar and compartmental regulation of dendritic growth in mature cortex. Nat Neurosci 12:116-8|