Riegle Kenneth C, Meyer Ronald L
Developmental and Cell Biology, University of California at Irvine, Irvine, California 92697, USA.
J Neurosci. 2007 Sep 26;27(39):10556-67. doi: 10.1523/JNEUROSCI.1631-07.2007.
Neurons may possess activity-dependent homeostatic mechanisms that permit them to globally alter synaptic strength as activity varies. We used the retinotectal projection of goldfish to test this idea in the intact adult CNS. We first altered tectal neuron activity by selectively manipulating excitatory input. When excitatory synaptic drive to tectal neurons was eliminated by blocking optic fibers, current evoked at optic synapses increased by 183% within 90 min. With partial activity blockade, the increase in synaptic strength scaled with the magnitude of activity depression. This silence-induced potentiation was also rapidly reversible. Conversely, an increase in optic input was followed by a decrease in evoked synaptic current. When optic drive was not altered and tectal neuronal activity was instead increased or decreased pharmacologically via GABA(A) receptors, synaptic strength again changed inversely with activity, indicating that synaptic strength changed in response to neuronal activity and not excitatory drive. Furthermore, altered synaptic strength tended to return ongoing activity to baseline. Changes in synaptic strength could also be detected in heterosynaptic pathways, indicating a global response. Finally, changes in synaptic strength were associated with corresponding changes in ongoing and evoked firing rates, indicating that the responsivity of tectal neurons was altered. Thus, tectal neurons exhibit archetypical homeostasis, one of the first robust examples in the intact adult CNS.
神经元可能拥有依赖于活动的稳态机制，使它们能够随着活动的变化全局改变突触强度。我们利用金鱼的视网膜顶盖投射在完整的成年中枢神经系统中测试了这一想法。我们首先通过选择性操纵兴奋性输入来改变顶盖神经元的活动。当通过阻断视神经纤维消除顶盖神经元的兴奋性突触驱动时，在90分钟内视神经突触处诱发的电流增加了183%。在部分活动阻断的情况下，突触强度的增加与活动抑制的程度成比例。这种沉默诱导的增强也是快速可逆的。相反，视神经输入增加后，诱发的突触电流会减少。当视神经驱动未改变，而是通过GABA(A)受体药理学上增加或减少顶盖神经元活动时，突触强度再次与活动呈反向变化，表明突触强度是对神经元活动而非兴奋性驱动做出反应。此外，改变的突触强度倾向于使持续活动恢复到基线水平。在异突触通路中也能检测到突触强度的变化，表明这是一种全局反应。最后，突触强度的变化与持续放电率和诱发放电率的相应变化相关，表明顶盖神经元的反应性发生了改变。因此，顶盖神经元表现出典型的稳态，这是完整成年中枢神经系统中最早的有力例证之一。
