The importance of volitional behavior in neuroplasticity.
The importance of volitional behavior in neuroplasticity.
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DOI：
10.1073/pnas.2208739119
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发表时间：
2022-07-26
影响因子：
11.1
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中科院分区：
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唐纳德·赫布（Donald Hebb）（1）甚至早在世纪前的威廉·詹姆斯（William James）（2）就提出了这样的假设：突触前和突触后活动之间的相关活动会导致两个神经元之间突触效能的加强，人们认为这是长期记忆形成的基础。高频刺激传入神经元和成对刺激突触前和突触后神经元诱导的长时程增强（LTP）是赫布形式的可塑性，从布利斯和Lomo（3）在海马（4）中的开创性工作开始，这种可塑性已得到广泛的实验验证。尖峰时间依赖性可塑性（STDP）通过证明突触前和突触后活动之间的精确时间可以导致突触的增强或抑制来完善这一想法（5）。然而，大多数诱导LTP和STDP的研究都集中在行为背景之外的突触可塑性。在PNAS中，Moorjani et al. (6)已经证明了一种使用电刺激的可塑性形式，其关键地取决于意志行为，并且已经表明，只要发生适当的意志行为，在诱导阶段之后，连接强度的变化可以维持甚至增强数天或甚至更长时间。Moorjani等人的研究中的关键见解。(6)是在非人灵长类动物的运动皮层（M1）中使用运动门控皮层内微刺激（ICMS），即使在电刺激结束后，该系统也可以进一步增强与正在进行的运动行为的连接。该方法涉及识别M1中表现出相互连接性的成对位点，通过一个位点的刺激触发诱发电位（EP）评估，由于另一个位点的单个测试刺激，这些位点表现出相互连接性。一个部位被指定为测试部位（称为Ntest），并且使用高频阈上刺激，基于在Ntest部位处的诱发肌电图（EMG）输出来训练猴子进行手腕运动（屈曲或伸展）（图1A）。例如，如果猴子的手腕部位的诱发肌电图输出是屈曲的，那么猴子就被要求自愿地屈曲手腕。同时，在Ntest的首选运动（例如，屈曲）期间，用ICMS以10 Hz刺激从Ntest接收功能连接的另一个部位（称为Nstim），使得Ntest部位附近的神经元可能正在放电，而Nstim部位附近的神经元之间同时发生诱导放电。因此，诱导阶段涉及Ntest和Nstim位点的神经元共激活，这与Hebbian可塑性一致。在运动门控刺激期间，基于EP振幅增加，Ntest和Nstim之间的功能连接增强，这是预期的（图1B）。然而，令人惊讶的是，刺激结束后，只要猴子继续进行与Ntest首选运动（例如，屈曲）相关的手腕运动，连接强度就会进一步增加（图1C和D）。进行适当的对照，以证明无进一步行为的运动门控刺激或无运动门控刺激的行为不会导致从Ntest到Nstim的功能连接增加。有趣的是，没有证据表明从Nstim到Ntest的反向功能连接增加。行为作为诱导可塑性的必要组成部分的作用并不完全是新的。在非人类灵长类动物的听觉皮层中使用不同的诱导范式，一系列研究发现，只有当动物被...
It was postulated by Donald Hebb (1) and even earlier over a century ago by William James (2) that correlated activity between pre-and postsynaptic activity would lead to strengthening of the synaptic efficacy between the two neurons, and it is believed to form the basis for long-term memory formation. Long-term potentiation (LTP) induced by high-frequency stimulation of afferents to a neuron and by paired stimulation of pre-and postsynaptic neurons are Hebbian forms of plasticity that have been experimentally validated extensively beginning with the seminal work of Bliss and Lomo (3) in the hippocampus (4). Spike timing–dependent plasticity (STDP) has refined this idea by demonstrating that the precise timing between pre-and postsynaptic activity can result in either potentiation or depression of the synapse (5). Nevertheless, most studies that have induced LTP and STDP have focused on synaptic plasticity outside of the context of behavior. In PNAS, Moorjani et al.(6) have demonstrated a form of plasticity using electrical stimulation that depends critically on volitional behavior and have shown that changes in connectivity strength can be maintained and even enhanced following the induction phase for days or even longer as long as the appropriate volitional behavior occurs. The key insight in the study by Moorjani et al.(6) is the use of movement-gated intracortical microstimulation (ICMS) in motor cortex (M1) of nonhuman primates that primed the system for further enhancement of connectivity with ongoing motor behavior even after electrical stimulation ended. The approach involved identifying paired sites in M1 that exhibited reciprocal connectivity as assessed by stimulus-triggered evoked potentials (EPs) at one site due to a single test stimulation at the other site. One site was designated as the test site (referred to as Ntest), and monkeys were trained to perform wrist movements (flexion or extension) based on the evoked electromyographical (EMG) output at the Ntest site using high-frequency suprathreshold stimulation (Fig. 1A). For example, monkeys were required to volitionally flex their wrist if the evoked EMG output of that site was flexion. At the same time, another site (referred to as Nstim) that received a functional connection from Ntest was stimulated with ICMS at 10 Hz during the preferred movement of Ntest (eg, flexion) such that neurons near the Ntest site were presumably firing, while induced firing occurred simultaneously among neurons near the Nstim site. Thus, the induction phase involved coactivation of neurons at Ntest and Nstim sites consistent with Hebbian plasticity. A strengthening in functional connectivity between Ntest and Nstim based on an amplitude increase of the EP occurred during movement-gated stimulation, which would be expected (Fig. 1B). What was striking, however, was that further increased connectivity strength occurred after stimulation ended as long as the monkeys continued to perform wrist movements associated with the preferred movement of Ntest (eg, flexion)(Fig. 1 C and D). Appropriate controls were performed to demonstrate that movement-gated stimulation without further behavior or behavior without movement-gated stimulation did not result in increases in functional connectivity from Ntest to Nstim. Interestingly, there was no evidence of increased functional connectivity in the reverse direction from Nstim to Ntest. The role of behavior as a necessary component in inducing plasticity is not entirely novel. Using a different induction paradigm in the auditory cortex of nonhuman primates, a series of studies found that inferred connectivity between two neurons increased only when animals were …
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影响因子：
56.9
作者：
AHISSAR, E;VAADIA, E;ABELES, M
通讯作者：
ABELES, M
影响因子：
11.2
作者：
Bütefisch, CM;Davis, BC;Cohen, LG
通讯作者：
Cohen, LG
影响因子：
5.5
作者：
BLISS, TVP;LOMO, T
通讯作者：
LOMO, T
影响因子：
3.7
作者：
Conner, J. M.;Kulczycki, M.;Tuszynski, M. H.
通讯作者：
Tuszynski, M. H.
DOI：
10.1073/pnas.2116321119
发表时间：
2022-07-05
影响因子：
11.1
作者：
通讯作者：
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