Dynamics and molecular mechanism of activity-dependent neuronal plasticity

在视皮层发育的关键期，单眼剥夺会导致神经元双眼反应的丧失和向睁眼的转移，这是一种正常的眼优势(OD)转移。然而，当MD与苍蝇酚对视皮层的慢性失活相结合时，神经元的OD分布向被剥夺的眼转移(反向OD移位)。我们先前已经证明，将蛋白激酶A(PKA)抑制剂8-氯腺苷-3-，5-环单硫代磷酸核糖异构体(RP-8-Cl-cAMPS)慢性注入猫视皮质，可消除正常的OD漂移。在这项研究中，我们研究了该抑制剂对OD反向移动的影响。将MD和Muscimol联合注射到6周大的猫咪的视皮层中，导致了OD值的反向移动，这与之前的研究中看到的情况相当。然而，在同时输注PKA抑制剂和麝香酚时，OD值也发生了反向变化。无论有无PKA抑制剂，在IV层观察到最强的OD漂移。这表明，突触前和突触后活动的分离，主要发生在丘脑皮质突触，导致了OD反向移动，而抑制PKA并不能阻止这一过程。据推测，抑制PKA对无声皮层没有影响。我们的结论是：1)PKA的激活不是诱导OD反向移动所必需的，2)MD诱导的OD可塑性的细胞内信号机制在正常和反向OD移动中是不同的。

Monocular deprivation (MD) during the critical period for the development of visual cortex causes a loss of binocular response of neurons and a shift to the open eye, a normal ocular dominance (OD) shift. However when MD is combined with chronic inactivation of the visual cortex by muscimol, the OD distribution of the neurons shifts to the deprived eye (reverse OD shift). We have previously shown that the normal OD shift is abolished by chronic infusion of the protein kinase A (PKA) inhibitor, 8-chloroadenosine-3_-, 5_--cyclic monophosphorothioate, Rpisomer (RP-8-Cl-cAMPS), into kitten visual cortex. In this study, we investigated the effect of this inhibitor on the reverse OD shift. Combination of MD and muscimol infusion into the visual cortex of 6-wk-old kittens caused a reverse OD shift that was comparable to that seen in previous studies. However, a reverse OD shift was also seen with concurrent infusion of the PKA inhibitor with muscimol. The strongest OD shift was observed in layer IV regardless of the presence or absence of the PKA inhibitor. This suggests that the dissociation of pre- and postsynaptic activities, which occurs mainly at thalamocortical synapses, induces the reverse OD shift and that inhibition of PKA does not prevent it. Presumably, an inhibition of PKA has no effect in silent cortex. We conclude that 1) an activation of PKA is not required for the induction of the reverse OD shift, and 2) the intracellular signaling mechanism underlying MD-induced OD plasticity differs between normal and reverse OD shifts.