We have developed a mouse model of visual system development which characterizes the structural and functional changes occurring between retinal ganglion cell axons and their postsynaptic targets in the lateral geniculate nucleus (LGN) of thalamus. While many of the changes in retinogeniculate axon patterning and connectivity have been described, a number of issues remain unresolved. For example we know little about the neural elements and intracellular signaling cascades that govern why certain retinal inputs are preserved and strengthened while others are weakened and eventually eliminated. While many of the inductive changes in connectivity rely on a spontaneous retinal activity and a Hebbian form of synaptic plasticity, the role of visually evoked activity and the synaptic plasticity associated with the maintenance of newly remodeled connections has not been fully explored. Detailed morphological information about the growth and maturation of retinogeniculate synapses and the dendrites of LGN relay cells is also needed to fully appreciate how the remodeling of retinal connections occurs. The major goals of this renewal is to use electrophysiological, anatomical, and biochemical techniques to detail the nature of L-type Ca2+ channel activity an event that appears essential for mediating activity dependent plasticity in LGN;to establish a link between L-type activity and the remodeling of retinogeniculate connections;to explore how alterations in visually evoked activity affect the maintenance of newly remodeled retinogeniculate connections;and to examine the dendritic morphology of developing LGN cells and determine how their structure-function relations are coordinated with the remodeling of retinal axons. Studies are done in wild-type pigmented mice as well as those in which L-type Ca2+ channel expression and activity has been severely attenuated by the targeted deletion of the ?3 subunit. The developing retinogeniculate pathway in the mouse has emerged as a powerful model system to study the mechanisms underlying the remodeling of synaptic connections. Therefore, these studies will provide valuable information about how the developing brain forms precise patterns of connections and offer further insight into the study and treatment of developmental and neurological disorders that result from the formation of abnormal patterns of connectivity.
These studies will provide valuable information about how the developing brain forms precise patterns of connections and offer further insight into the study and treatment of developmental and neurological disorders that result from the formation of abnormal patterns of connectivity.
|Hammer, Sarah; Carrillo, Gabriela L; Govindaiah, Gubbi et al. (2014) Nuclei-specific differences in nerve terminal distribution, morphology, and development in mouse visual thalamus. Neural Dev 9:16|
|Kuwajima, Takaaki; Sitko, Austen A; Bhansali, Punita et al. (2013) ClearT: a detergent- and solvent-free clearing method for neuronal and non-neuronal tissue. Development 140:1364-8|
|Chen, Shih-Kuo; Chew, Kylie S; McNeill, David S et al. (2013) Apoptosis regulates ipRGC spacing necessary for rods and cones to drive circadian photoentrainment. Neuron 77:503-15|
|Fitting, Sylvia; Ignatowska-Jankowska, Bogna M; Bull, Cecilia et al. (2013) Synaptic dysfunction in the hippocampus accompanies learning and memory deficits in human immunodeficiency virus type-1 Tat transgenic mice. Biol Psychiatry 73:443-53|
|Seabrook, Tania A; El-Danaf, Rana N; Krahe, Thomas E et al. (2013) Retinal input regulates the timing of corticogeniculate innervation. J Neurosci 33:10085-97|
|Brooks, Justin M; Su, Jianmin; Levy, Carl et al. (2013) A molecular mechanism regulating the timing of corticogeniculate innervation. Cell Rep 5:573-81|
|Krahe, Thomas E; Seabrook, Tania A; Chen, Ching-Kang J et al. (2012) Modulation of CREB in the dorsal lateral geniculate nucleus of dark-reared mice. Neural Plast 2012:426437|
|Dilger, Emily K; Shin, Hee-Sup; Guido, William (2011) Requirements for synaptically evoked plateau potentials in relay cells of the dorsal lateral geniculate nucleus of the mouse. J Physiol 589:919-37|
|McNeill, David S; Sheely, Catherine J; Ecker, Jennifer L et al. (2011) Development of melanopsin-based irradiance detecting circuitry. Neural Dev 6:8|
|Fox, Michael A; Guido, William (2011) Shedding light on class-specific wiring: development of intrinsically photosensitive retinal ganglion cell circuitry. Mol Neurobiol 44:321-9|
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