Dynamics and molecular mechanism of activity-dependent neuronal plasticity

在视觉皮层发育的关键时期，单眼剥夺（MD）会导致双眼神经元反应的丧失和正常的眼优势（OD）转移。然而，当MD合并muscimol对视觉皮层的慢性失活时，神经元的OD分布转移到被剥夺的眼睛（反向OD转移）。我们之前的研究表明，将蛋白激酶A （PKA）抑制剂8-氯腺苷-3_-，5_-环单磷硫酸酯聚合体（RP-8-Cl-cAMPS）长期输注到小猫视觉皮层中，可以消除正常的OD位移。在这项研究中，我们研究了这种抑制剂对反向OD位移的影响。将MD和muscimol输注到6周龄小猫的视觉皮层中，引起了与先前研究相当的反向OD变化。然而，当PKA抑制剂与muscimol同时输注时，也可以观察到相反的OD变化。无论PKA抑制剂是否存在，在第4层观察到最强的OD位移。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，诱导了反向的OD移动，而PKA的抑制并不能阻止它。据推测，PKA的抑制对沉默皮层没有影响。我们得出的结论是：1)PKA的激活不需要诱导OD的反向移位；2)md诱导的OD可塑性的细胞内信号机制在正常和反向OD移位之间是不同的。

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.