神经刺激方案越来越多地用作治疗干预措施,包括脑损伤.除了神经元的直接激活,这些刺激方案也可能对这些神经元的突触输出产生下游影响。众所周知,突触连接强度的改变(长期增强,LTP;长期抑郁,LTD)对用于诱导的刺激频率敏感,然而,关于刺激的时间模式对下游突触可塑性的贡献知之甚少,这可能是由神经刺激在受伤的大脑中引起的。我们探索了正常大脑皮层和轻度创伤性脑损伤(mTBI)后神经刺激的时间模式和频率的相互作用,告知治疗以加强或削弱受伤大脑的神经回路,以及更好地了解这些因素在正常大脑可塑性中的作用。单个神经元中诱发的突触后电位(PSP)的全细胞(WC)膜片钳记录,以及场电位(FP)记录,由视觉皮层的2/3层制成,以响应第4层的刺激,在来自对照的急性切片中(幼稚),假手术,和mTBI大鼠。我们比较了不同刺激方案诱导的突触可塑性,每个由特定频率(1Hz,10Hz,或100Hz),连续性(连续或不连续),和时间模式(完全规则,有点不规则,或高度不规则)。在单个神经元水平,当在1Hz或10Hz下使用高度不规则的刺激方案时,可塑性结果出现了巨大差异,在控件和Shams中生产整体LTD,但mTBI后总体LTP强劲。与单个神经元的结果一致,同时FP记录的可塑性结果相似,表明我们的结果推广到比单独的WC记录可以采样的更大规模的突触网络。除了在可塑性结果之间的差异控制(幼稚或假)和受伤的大脑,刺激过程中发生的突触反应变化的动力学可以预测最终的可塑性结果.我们的结果表明,刺激的时间模式在大脑皮层中诱导的突触可塑性的极性和幅度中起作用,同时突出了正常和受伤的大脑反应之间的差异。此外,这些结果可能有助于优化神经刺激疗法以治疗mTBI和其他脑部疾病,除了为正常大脑的下游可塑性信号机制提供新的见解。
Neurostimulation protocols are increasingly used as therapeutic interventions, including for brain injury. In addition to the direct activation of neurons, these stimulation protocols are also likely to have downstream effects on those neurons\' synaptic outputs. It is well known that alterations in the strength of synaptic connections (long-term potentiation, LTP; long-term depression, LTD) are sensitive to the frequency of stimulation used for induction; however, little is known about the contribution of the temporal pattern of stimulation to the downstream synaptic plasticity that may be induced by neurostimulation in the injured brain. We explored interactions of the temporal pattern and frequency of neurostimulation in the normal cerebral cortex and after mild traumatic brain injury (mTBI), to inform therapies to strengthen or weaken neural circuits in injured brains, as well as to better understand the role of these factors in normal brain plasticity. Whole-cell (WC) patch-clamp recordings of evoked postsynaptic potentials in individual neurons, as well as field potential (FP) recordings, were made from layer 2/3 of visual cortex in response to stimulation of layer 4, in acute slices from control (naive), sham operated, and mTBI rats. We compared synaptic plasticity induced by different stimulation protocols, each consisting of a specific frequency (1 Hz, 10 Hz, or 100 Hz), continuity (continuous or discontinuous), and temporal pattern (perfectly regular, slightly irregular, or highly irregular). At the individual neuron level, dramatic differences in plasticity outcome occurred when the highly irregular stimulation protocol was used at 1 Hz or 10 Hz, producing an overall LTD in controls and shams, but a robust overall LTP after mTBI. Consistent with the individual neuron results, the plasticity outcomes for simultaneous FP recordings were similar, indicative of our results generalizing to a larger scale synaptic network than can be sampled by individual WC recordings alone. In addition to the differences in plasticity outcome between control (naive or sham) and injured brains, the dynamics of the changes in synaptic responses that developed during stimulation were predictive of the final plasticity outcome. Our results demonstrate that the temporal pattern of stimulation plays a role in the polarity and magnitude of synaptic plasticity induced in the cerebral cortex while highlighting differences between normal and injured brain responses. Moreover, these results may be useful for optimization of neurostimulation therapies to treat mTBI and other brain disorders, in addition to providing new insights into downstream plasticity signaling mechanisms in the normal brain.