Barbara Gordon

The role of norepinephrine in plasticity of visual cortex.

Abbreviations

The effect of age on binding of MK-801 in the cat visual cortex

We have examined the effect of age on the binding of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate (MK-801) in the cat visual cortex. We hypothesized that this binding might change with age because: (1) MK-801 binds to a site associated with the N-methyl-D-aspartate (NMDA) receptor; (2) the NMDA receptor complex has been implicated in neural plasticity; (3) plasticity in the cat visual cortex is age dependent. We used standard receptor binding techniques to measure MK-801 binding in membrane homogenates in cats aged 7 days (d), 21 d, 43 d, 83 d, 7-8 months (mo) and over 2 years. Glutamate (100 microM), glycine (30 microM) and spermidine (20 microM) were used to enhance binding. We found that MK-801 binding is maximal at about 6 weeks of age, decreases slightly by 83 days and then decreases more dramatically in adults. Saturation analysis showed that the of binding with age resulted from variation in number of binding sites and not from variation in affinity. The ability of Mg2+ to inhibit MK-801 binding did not change with age. Dark rearing did not alter the development of MK-801 binding sites.

Postnatal development of NR1, NR2A and NR2B immunoreactivity in the visual cortex of the rat

N-Methyl-D-aspartate receptors (NMDARs) are critically involved in some types of synaptic plasticity. The NMDAR subunits NR1, NR2A and NR2B are developmentally regulated, and it has been proposed that developmental changes in their expression may underlie developmental changes in cortical plasticity. Age-dependent change in cortical plasticity is most commonly measured by the monocular deprivation effect, which occurs during a critical period between P22 and P50 in the rat. Although the development of NMDAR subunits has been studied from birth through the fourth postnatal week, there is only meager information from older ages when visual plasticity ends. We hypothesized that there will be significant age-dependent change in expression of NR1, NR2A or NR2B between P22, when the cortex is plastic, and P90, when it is not. We applied specific antibodies recognizing NR1, NR2A and NR2B to the primary visual cortex at P14, P22, P30, P45 and P90. We found age-dependent changes in NR1-IR that were negatively correlated with changes in NR2A-IR; these subunits are not regulated in unison. In contrast, NR2A-IR and NR2B-IR were positively correlated. NR2A-IR and NR2B-IR both passed through a developmental minimum around P45, then recovered to approximately their P22 level. NR1-IR passed through a maximum at P45. There were no significant differences between P22 and P90. These results do not support the simple hypothesis that the loss of plasticity corresponds to a simple transition from juvenile levels of NMDAR subunit proteins to new adult levels. On the other hand, the results do confirm the hypothesis that there are significant changes in processing of NMDAR proteins during the time that plasticity is lost. How these changes of IR relate to synaptic transmission and plasticity needs to be clarified.

Swept contrast visual evoked potentials and their plasticity following monocular deprivation in mice.

The swept contrast visual evoked potential technique is a quasi-psychophysical method that can help bridge the gap between cell biology and visual performance in studies of ocular dominance plasticity. In mice we found that four days of monocular deprivation diminished the amplitude of evoked potentials from the deprived eye relative to the non-deprived eye. This ocular dominance plasticity was nearly as great in adult mice as in juveniles. The monocular deprivation effect was mediated, at least in part, by enhancement of responses evoked from the non-deprived eye, rather than by depression of responses from the deprived eye.

Development of NR1, NR2A and NR2B mRNA in NR1 immunoreactive cells of rat visual cortex

In cells marked for N-methyl-D-aspartate receptors (NMDARs), we studied the relationship between the sensitive period for monocular deprivation and the expression of rat NMDAR subunits, NR2A and NR2B. In the rat the sensitive period ends sometime after postnatal day 50 (P50). Previous studies of the development of these subunit mRNAs focused on animals prior to the end of the sensitive period and did not examine the visual cortex specifically. We used a monoclonal antibody to the NR1 subunit of the receptor to identify cells containing NMDARs. We then used in situ hybridization to label the same sections for NR2A or NR2B mRNA. In an additional experiment we labeled sections for NR1 mRNA to see if the developmental profile was similar at both the mRNA and protein level. We used five animals at each of four ages: P22, P30, P45 and P90. Staining for NR2B mRNA, but not for NR2A mRNA, decreased dramatically from P22 to P45. Staining for NR1 mRNA declined dramatically between P22 and P45 even though most cells remained strongly immunopositive for the NR1 protein during this time. This discrepancy suggests that significant NR1 regulation occurs after gene transcription. Because most of the decrease in NR1 mRNA and NR2B mRNA occurs by P30, transcriptional regulation of these subunits does not easily explain the loss of sensitivity to monocular deprivation, which occurs around P50. The changes are, in fact, more closely synchronized with the beginning of experience-dependent plasticity than with its end.

Long term visual deprivation in a human

D.C. had a congenital monocular cataract removed at 19 years of age. Preoperatively, he was virtually blind in the deprived eye. By 4 months after surgery he could resolve about 1.4 c/deg by acuity did not improve further over the next 7 months. Immediately postoperatively, the temporal retina was blind, but over the next 4 months its visual field increased to 20. The temporal retina continued, however, to have elevated thresholds. D.C. also exhibited a peculiar form of binocular competition. Thresholds of the deprived binocular portions of the nasal retina were greatly elevated by light falling on the non-deprived eye. Visual function in the non-deprived eye was normal.

Critical period and minimum exposure required for the effects of alternating monocular occlusion in cat visual cortex

Abstract The time course of the effects of alternating monocular occlusion was studied in two experiments. First, alternating monocular occlusion was begun at 5 weeks of age and continued for 1, 2. 10 or 21 days. A clear decrease in the proportion of binocular cells in the visual cortex was observed in animals subjected to alternating occlusion for 10 or 21 days, but not in animals exposed for 1 or 2 days, Second, alternating occlusion for 21 days was begun at 5, 8 or 12 weeks of age or in adulthood. Cortical binocularity decreased only when alternating occlusion began at 5 or 8 weeks of age.

Orientation deprivation in cat: What produces the abnormal cells?

SummaryWhen an animal is reared with goggles containing stripes of a single orientation, many cells in the visual cortex become abnormal. To find out whether these abnormal cells result from orientation deprivation per se or from other features of goggle rearing we reared kittens with goggles containing stripes of many orientations. The data suggest that orientation deprivation contributes to the development of abnormal cells but is not its sole cause.

Visual behavior of monocularly deprived kittens treated with 6-hydroxydopamine.

Several investigators have reported that treating the visual cortex with 6-hydroxydopamine (6-OHDA) preserves the ability of a monocularly deprived eye to drive cells in the visual cortex. If 6-OHDA provides useful protection from the effects of monocular deprivation, it should also prevent the behavioral blindness that normally accompanies monocular deprivation. To test this prediction we compared the visual behavior of monocularly deprived kittens pretreated with 6-OHDA with that of kittens similarly deprived, but not drug-treated. Kittens were trained on a visual discrimination task before drug treatment or suture. Starting at about 5 weeks of age the kittens were given 6-OHDA via ventricular cannula, given vehicle solution, or given no treatment at all. At about 6 weeks of age all kittens were monocularly deprived for one week. When the deprived eye was opened at 7 weeks of age, most kittens not receiving 6-OHDA were blind when tested with the deprived eye. In contrast, none of the kittens receiving 6-OHDA intraventricularly were blind when tested with the deprived eye. 6-OHDA had no effect on performance with the non-deprived eye. We conclude that 6-OHDA protects vision through the monocularly deprived eye without impairing vision through the non-deprived eye.

The development of MK-801, kainate, AMPA, and muscimol binding sites in cat visual cortex.

Previous work using homogenate binding has shown that the development of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10imin e maleate (MK-801) binding in cat visual cortex increases from 21 days to 42 days, the height of the plastic period, and decreases in adulthood. We have studied the generality of this finding by examining the development of NMDA binding sites in several brain regions and by examining the development of other binding sites in the visual cortex. After confirming the original finding, we extended it by showing that the sensitivity of MK-801 binding sites to glutamate and glycine decreases when the cat becomes an adult. We then examined the regional specificity of MK-801 binding. Retinal binding did not change significantly with age. Binding in both visual cortex and hippocampus increased significantly from 7 days to 42 days regardless of whether binding was measured per milligram wet weight or per milligram protein. The decline from 42 days to adulthood was less dramatic in the hippocampus than in the visual cortex and was statistically significant only when binding was measured per milligram protein. Saturation analyses also showed a difference in the two structures. Bmax in the visual cortex, but not in the hippocampus, decreased from 42 days to adulthood. To determine whether these developmental changes were specific to MK-801 binding sites, we compared the age-dependent binding of MK-801, kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and muscimol. Like MK-801, kainate binding increased from 7 days to 42 days and decreased from 42 days to adulthood. AMPA and muscimol binding showed a similar increase in binding from 7 days to 42 days but did not decrease significantly from 42 days to adulthood. Displacement experiments suggest that AMPA and kainate bind to separate sites. The 42-day peak in NMDA and kainate binding suggests that their associated receptors may have a role in determining the plastic period of visual cortex.