Concentration-dependent suppression by β-adrenergic antagonists of the shift in ocular dominance following monocular deprivation in kitten visual cortex

Abstract

We showed that β-adrenergic receptor antagonists blocked the shift in ocular dominance following brief monocular deprivation in young kittens. Localized microperfusion of propranolol into the kitten visual cortex reduced the expected shift in the ocular dominance ~2 mm away from the center of perfusion. The blocking effect, however, did not reach an area ~5 mm from the perfusion center, suggesting that β blockers work in a concentration-dependent fashion in the present paradigm. We further studied the concentration-effect relationship by widely changing the concentration of β blockers (propranolol and sotalol) stored in an osmotic minipump. The proportion of binocular cells increased from 0.13 to 0.67 when the concentration of propranolol was increased from 10 −6 M to 10 −2 M, giving the half-maximum effect (binocularity, 0.40) at about 10 −4 M propranolol. However, the maximum binocularity obtained with the sotalol perfusion under the comparable condition was apparently much lower (0.45) than that with propranolol. Accordingly, the half-maximum binocularity (0.30) was obtained at about 10 −5 M sotalol. We also noted the presence of a linear, inverse relation between the logarithmic concentration of the β blockers and the extent of the shift in ocular dominance as measured by the proportion of monocular cells which responded exclusively to stimulation of the nondeprived eye. The latter decreased from 0.75 to 0.25, when the former was increased from 10 −6 M to 10 −2 M (in an osmotic minipump). The two β blockers behaved similarly in this correlation. The intracortical spread of locally perfused [ 3H]propranolol was studied at the end of the cortical perfusion which lasted for a week. The radioactivity was highest at the perfusion center and rapidly declined with increasing distance, leveling off ~3 mm from the perfusion center. The average “dilution factor” of locally perfused [ 3H]propranolol was calculated as about 11/70 of the original solution in an area of physiological recordings (~2 mm from the perfusion center). Applying the “dilution factor” of 11/70, we estimated the approximate concentration of β blockers needed at the recording sites to obtain the half-maximum effect; it was about 5.8 × 10 −7M for propranolol and 5.8 × 10 −8M for sotalol. Taken together, the present results were interpreted as suggesting that there is a positive correlation between the number of activated β-adrenergic receptors within the visual cortex and the extent of changes in ocular dominance following monocular deprivation. Thus, we conclude that normally functioning β-adrenergic receptors may be critically involved in the regulation of visuocortical plasticity.