Neural activity is believed to play a central role in functional synaptic maturation. This hypothesis will be tested using a mouse retinogeniculate slice prep, performing in vivo presynaptic activity manipulations. The normal timecourse of strengthening and afferent pruning following eye-opening has already been characterized at this synapse. The first specific aim will test the role of visually evoked retinal activity in promoting maturation of retinogeniculate synapses. Presynaptic activity will be manipulated by light rearing, dark rearing, and strobe rearing. The second specific aim will distinguish the contribution of different sources of activity to synaptic strengthening and pruning by intraocular injection of drugs. Pharmacologically, total blockade can be achieved with TTX, while epibatidine can specifically block spontaneous retinal waves. Increases in activity will be stimulated with forskolin. Thus, the contributions of patterned visual activity after eye opening and spontaneous retinal waves activity to the refinement of this connection will be isolated. The use of this model in mouse wilt permit later work on molecular and genetic components to neural circuit construction, as well as possible insight into neonatal neurological disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS048630-02
Application #
6874460
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Talley, Edmund M
Project Start
2004-03-01
Project End
2007-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
2
Fiscal Year
2005
Total Cost
$30,190
Indirect Cost
Name
Harvard University
Department
Biology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Papale, Andrew E; Hooks, Bryan M (2018) Circuit changes in motor cortex during motor skill learning. Neuroscience 368:283-297
Louros, Susana R; Hooks, Bryan M; Litvina, Liza et al. (2014) A role for stargazin in experience-dependent plasticity. Cell Rep 7:1614-1625
Hauser, Jessica L; Edson, Eleanore B; Hooks, Bryan M et al. (2013) Metabotropic glutamate receptors and glutamate transporters shape transmission at the developing retinogeniculate synapse. J Neurophysiol 109:113-23
Hooks, Bryan M; Chen, Chinfei (2008) Vision triggers an experience-dependent sensitive period at the retinogeniculate synapse. J Neurosci 28:4807-17
Roy, Kristine; Murtie, Joshua C; El-Khodor, Bassem F et al. (2007) Loss of erbB signaling in oligodendrocytes alters myelin and dopaminergic function, a potential mechanism for neuropsychiatric disorders. Proc Natl Acad Sci U S A 104:8131-6
Hooks, Bryan M; Chen, Chinfei (2006) Distinct roles for spontaneous and visual activity in remodeling of the retinogeniculate synapse. Neuron 52:281-91