Kasamatsu T, Imamura K, Mataga N, Hartveit E, Heggelund U, Heggelund P
Smith-Kettlewell Eye Research Institute, San Francisco, CA 94115, USA.
Neuroscience. 1998 Feb;82(3):687-700. doi: 10.1016/s0306-4522(97)00222-4.
We have re-examined whether N-methyl-D-aspartate receptors play a specific role in experience-dependent plasticity in kitten visual cortex. A specific antagonist of this glutamate receptor subtype, D,L-2-amino-5-phosphonovaleric acid, was directly and continuously infused into kitten striate cortex for one week concurrently with monocular lid suture. In the hemisphere infused with 50 mM antagonist, we found the usual shift in ocular dominance toward the open eye with only a few binocular cells remaining. The changes were accompanied by an extremely high incidence (38%) of abnormal cells lacking orientation selectivity across different ocular dominance groups. In kitten cortex infused with 10 mM antagonist concurrently with monocular deprivation for a week, recording from a drug-affected region near the infusion centre, we again found the U-shaped ocular dominance distribution with the high incidence of non-selective cells. In antagonist-infused, otherwise normal striate cortex of adult cats, we found that the proportion of binocular cells decreased by one-half in two cellular populations: one recorded during the continuous infusion of 10 mM antagonist under general anaesthesia and paralysis, and the other about two days after stopping the infusion. We also established that in vivo concentrations of chronically infused 10 mM antagonist decreased, not near-exponentially, but linearly with increasing distance from the infusion site. Thus, the effects of a directly and continuously infused, concentrated antagonist of N-methyl-D-aspartate receptors on receptive-field properties of visuocortical cells are complex. The present findings strongly suggest that the antagonist effects in the developing cortex may be due primarily to blockade of normal synaptic transmission rather than specific disruption of an experience-dependent mechanism underlying ocular dominance plasticity.
我们重新研究了N-甲基-D-天冬氨酸受体在小猫视觉皮层依赖经验的可塑性中是否发挥特定作用。这种谷氨酸受体亚型的特异性拮抗剂D，L-2-氨基-5-磷酸戊酸在单眼眼睑缝合的同时，被直接连续注入小猫的纹状皮层一周。在注入50 mM拮抗剂的半球中，我们发现眼优势通常向睁开的眼睛转移，仅剩下少数双眼细胞。这些变化伴随着不同眼优势组中缺乏方向选择性的异常细胞的极高发生率（38%）。在注入10 mM拮抗剂并同时进行单眼剥夺一周的小猫皮层中，从注入中心附近受药物影响的区域进行记录，我们再次发现了U形的眼优势分布以及非选择性细胞的高发生率。在注入拮抗剂的成年猫原本正常的纹状皮层中，我们发现在两个细胞群体中，双眼细胞的比例下降了一半：一个群体是在全身麻醉和麻痹状态下连续注入10 mM拮抗剂期间进行记录的，另一个群体是在停止注入约两天后进行记录的。我们还确定，长期注入10 mM拮抗剂的体内浓度不是近似指数下降，而是随着与注入部位距离的增加呈线性下降。因此，直接连续注入的N-甲基-D-天冬氨酸受体浓缩拮抗剂对视皮层细胞感受野特性的影响是复杂的。目前的研究结果强烈表明，在发育中的皮层中拮抗剂的作用可能主要是由于正常突触传递的阻断，而不是对视皮层优势可塑性潜在的依赖经验机制的特异性破坏。
