The long-term goal of our study is to identify cellular and molecular bases for the unique sensitivity of immature cortical cells to visual experience early in postnatal life. Understanding the critical period plasticity in the cat model may help to elucidate neural mechanisms underlying amblyopia ex anopsia. Taking advantage of plasticity-enhancing effects of 1-noradrenaline (1- NA) directly infused into aplastic visual cortex of anesthetized and paralyzed kittens, we want to explore a new strategy with which we can quickly alter ocular dominance of individual cells. In response to new evidence which suggests the involvement of postsynaptic activity- dependent mechanisms in the matter, likely interactions among such the mechanisms and the NA-B adrenoreceptor system within visual cortex will be sought in chronic kittens. Another chronic study will be made to gain insight into possible target molecules which may integrate both B adrenoreceptor - and muscarinic receptor-dependent processes int eh regulation of cortical plasticity. We also want to carry out a thorough study on regenerative NA terminals in cat visual cortex, addressing a broad neuroscience question of regeneration of CNS axons. We will study in the 1-NA-infused cortex of anesthetized and paralyzed kittens 1) time courses of changes in binocularity response to optically induced squint at various time intervals before and during receptive-field mappings, as a population and on the single-cell basis (""""""""on-line"""""""" modification), 2) functional cell types (simple, complex and hyercomplex with end-stopping properties), laminar location of every recorded cell, and its relation to the center of the nearest ocular dominance patches which are visualized histologically. In the similar context as above, we will study the plasticity-enhancing effect of electrical stimulation delivered to the NA cells in the locus coeruleus. 3) By locally infusing muscimol into a cortical area affected by a preceding (no temporal overlap) infusion with propranolol, we will study whether the expression of the """"""""muscimol effects"""""""" is dependent on the function of the NA-B adrenoreceptor system. 4) We will confirm and extend our preliminary results that a shift in ocular dominance following brief monocular lid suture in kittens is blocked by repeated i.p. injections of Li2 CO3. 5) We will also study the presence of genuine regenerative NA terminals in the-6-hydroxydopamine-infused visual cortex of adult cats using a multidisciplinary approach.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006733-04
Application #
3263341
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1986-04-01
Project End
1994-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Smith-Kettlewell Eye Research Institute
Department
Type
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94115
Kasamatsu, T; Schmidt, E K (1997) Continuous and direct infusion of drug solutions in the brain of awake animals: implementation, strengths and pitfalls. Brain Res Brain Res Protoc 1:57-69
Nakai, K; Niiyama, K; Kasamatsu, T et al. (1994) Regeneration of norepinephrine-containing fibers in occipital cortex of adult cats. Brain Res Bull 35:409-12