Doses of 6-hydroxydopamine sufficient to deplete norepinephrine are not sufficient to decrease plasticity in the visual cortex

Abstract

These experiments were designed to test Kasamatsu and Pettigrew's (1979, 1983, and see below) hypothesis that plasticity in the visual cortex requires cortical norepinephrine (NE). Kittens were treated with various doses of intraventricular 6-hydroxydopamine (6-OHDA) or vehicle solution. Cortical NE content was measured with high-performance liquid chromatography with electrochemical detection. We sutured the right eyes of some kittens approximately 6 weeks of age for 1 week and recorded from the left visual cortex of these kittens at the end of the week of suture. We measured the ability of the deprived eye to drive cortical cells in animals that received either 0.2 or 4.8 mg of 6-OHDA, and also in control animals that received only vehicle solution. We concluded that a particular dose of 6-OHDA decreased plasticity if it increased (relative to controls) the ability of the deprived eye to drive cortical cells. Doses of 6-OHDA as small as 0.2 mg were sufficient to produce approximately maximal depletion of NE but did not decrease cortical plasticity. Doses of 4.8 mg or more did decrease cortical plasticity, although not as much as was reported by Kasamatsu and Pettigrew. We conclude that 6-OHDA can alter cortical plasticity but the decrease in plasticity does not result from NE depletion.

Release of cortical catecholamines by visual stimulation requires activity in thalamocortical afferents of monkey and cat

“…No changes in the monitored baseline currents were observed for strobe or radial grating stimulation or any other stimuli presented. Tissue levels of NE and DA were found to be reduced by about 80% of their normal physiological values, within the range previously reported for 6-OHDA administration (Kasamatsu and Pettigrew, 1979;Daw et al, 1984;Trombley et al, 1986). Thus, our data suggest that oxidation currents were due to NE/DA only and that visually evoked release required NE/DA in amounts greater than 20% of the normal endogenous levels.…”

“…We have shown previously that the DA contribution to electrochemically monitored changes in extracellular NE concentrations in rat cerebral cortex is negligible (HowardButcher et al, 1985). In cats, NE tissue concentrations are about 2.5 times those of DA (Trombley et al, 1986).…”

“…To be certain that the graphite-paste recording electrode was sensing oxidation currents from NE and DA only, we pretreated one cat with 4 daily injections of 1.8 mg of the CA neurotoxin 6-hydroxydopamine (6-OHDA; 7 mg total dose). The drug was delivered through a surgically implanted intraventricular cannula following the protocol of Trombley et al (1986). Subsequent histological examination showed the cannula to be in the third ventricle, and a black precipitate was present on the walls of the third and fourth ventricles of both hemispheres.…”

“…Tissue levels of NE and DA were measured by high-performance liquid chromatography with electrochemical detection (Trombley et al, 1986).…”

“…Kasamatsu and colleagues (Kasamatsu and Pettigrew, 1979;Itakura et al, 1981;Kasamatsu and Heggelund, 1982) have argued that NE may maintain the binocularity of neurons in kitten striate cortex following monocular deprivation. The conclusions from these studies have been called into question by several laboratories (e.g., Adrien et al, 1985;Trombley et al, 1986).…”