Epilepsy Research Laboratory, Department of Neurological Surgery and Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, CA 94143.
Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):492-7. doi: 10.1073/pnas.1307784111. Epub 2013 Dec 16.
Chronic changes in excitability and activity can induce homeostatic plasticity. These perturbations may be associated with neurological disorders, particularly those involving loss or dysfunction of GABA interneurons. In distal-less homeobox 1 (Dlx1(-/-)) mice with late-onset interneuron loss and reduced inhibition, we observed both excitatory synaptic silencing and decreased intrinsic neuronal excitability. These homeostatic changes do not fully restore normal circuit function, because synaptic silencing results in enhanced potential for long-term potentiation and abnormal gamma oscillations. Transplanting medial ganglionic eminence interneuron progenitors to introduce new GABAergic interneurons, we demonstrate restoration of hippocampal function. Specifically, miniature excitatory postsynaptic currents, input resistance, hippocampal long-term potentiation, and gamma oscillations are all normalized. Thus, in vivo homeostatic plasticity is a highly dynamic and bidirectional process that responds to changes in inhibition.
兴奋性和活动的慢性变化可诱导同型稳态可塑性。这些干扰可能与神经紊乱有关，尤其是涉及 GABA 中间神经元缺失或功能障碍的神经紊乱。在 Dlx1(-/-)晚发性中间神经元缺失和抑制减少的小鼠中，我们观察到兴奋性突触抑制和内在神经元兴奋性降低。这些同型稳态变化并不能完全恢复正常的回路功能，因为突触抑制导致长时程增强和异常γ振荡的可能性增强。通过移植内侧神经节隆起中间神经元祖细胞引入新的 GABA 能中间神经元，我们证明了海马功能的恢复。具体而言，微小的兴奋性突触后电流、输入电阻、海马体长时程增强和γ振荡都恢复正常。因此，体内同型稳态可塑性是一种高度动态和双向的过程，可对抑制的变化做出反应。
