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.
