Neuronal activity is important for development of eye-specific segregation and cortical cell orientation specificity in the mammalian visual system. The proposed studies will block or change retinal activity using pharmacological agents or immunotoxins in developing ferrets. Results will show effects of altered patterns of activity on the establishment and maintenance of neuronal connections, of changes in the connection patterns. The first set of experiments (Aim 1) will look quantitatively at the normal time course of segregation of afferents from the two eyes in the lateral geniculate nucleus (LGN), and will determine whether activity blockade during the period of initial segregation actually prevents segregation or causes desegregation or both. The second set of experiments (Aim 2) will determine the effects of removing the normal pattern retinal ganglion cell activity (synchronized bursts of action potentials in neighboring ganglion cells) on the development of receptive field properties in LGN and primary visual cortex. In the third set of experiments (Aim 3), the initial normal segregation of axons from the two eyes will be prevented by activity blockade from PND 1-10, and then the animals will be allowed a period of recovery, resulting in LGNs where the axons from the two eyes are completely segregated, but normal laminae do not form. The effects of this altered retinogeniculate projection on the physiology of single ceils and on functional organization in the primary visual cortex will be studied using electrophysiological recordings, optical imaging, and transneuronal labeling. This will help to determine whether normal lamination of eye-specific inputs in the LGN is necessary for normal visual function. The final series of experiments (Aims 4 and 5) will look at the effects on cortical cell receptive fields of removing ON-center activity during development. Results from these experiments will show how patterns of activity may be involved in developing receptive field properties. The proposed experiments should further our knowledge of the rules of activity-dependent development, and the consequences of disrupting connections; this may have implications for human developmental disorders.
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