Mowery Todd M, Garraghty Preston E
Department of Otolaryngology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ, United States.
Department of Psychological and Brain Sciences, Indiana University Bloomington, Bloomington, IN, United States.
Front Syst Neurosci. 2023 Jan 24;16:1086680. doi: 10.3389/fnsys.2022.1086680. eCollection 2022.
Although neural plasticity is now widely studied, there was a time when the idea of adult plasticity was antithetical to the mainstream. The essential stumbling block arose from the seminal experiments of Hubel and Wiesel who presented convincing evidence that there existed a critical period for plasticity during development after which the brain lost its ability to change in accordance to shifts in sensory input. Despite the zeitgeist that mature brain is relatively immutable to change, there were a number of examples of adult neural plasticity emerging in the scientific literature. Interestingly, some of the earliest of these studies involved visual plasticity in the adult cat. Even earlier, there were reports of what appeared to be functional reorganization in adult rat somatosensory thalamus after dorsal column lesions, a finding that was confirmed and extended with additional experimentation. To demonstrate that these findings reflected more than a response to central injury, and to gain greater control of the extent of the sensory loss, peripheral nerve injuries were used that eliminated ascending sensory information while leaving central pathways intact. Merzenich, Kaas, and colleagues used peripheral nerve transections to reveal unambiguous reorganization in primate somatosensory cortex. Moreover, these same researchers showed that this plasticity proceeded in no less than two stages, one immediate, and one more protracted. These findings were confirmed and extended to more expansive cortical deprivations, and further extended to the thalamus and brainstem. There then began a series of experiments to reveal the physiological, morphological and neurochemical mechanisms that permitted this plasticity. Ultimately, Mowery and colleagues conducted a series of experiments that carefully tracked the levels of expression of several subunits of glutamate (AMPA and NMDA) and GABA (GABAA and GABAB) receptor complexes in primate somatosensory cortex at several time points after peripheral nerve injury. These receptor subunit mapping experiments revealed that membrane expression levels came to reflect those seen in early phases of critical period development. This suggested that under conditions of prolonged sensory deprivation the adult cells were returning to critical period like plastic states, i.e., developmental recapitulation. Here we outline the heuristics that drive this phenomenon.
尽管神经可塑性如今已得到广泛研究，但曾有一段时间，成体可塑性的观点与主流观点背道而驰。关键的绊脚石源于休伯尔和威塞尔的开创性实验，他们提供了令人信服的证据，表明在发育过程中存在一个可塑性的关键期，在此之后，大脑失去了根据感觉输入变化而改变的能力。尽管当时的思潮认为成熟大脑相对不易改变，但科学文献中还是出现了一些成体神经可塑性的例子。有趣的是，其中一些最早的研究涉及成年猫的视觉可塑性。更早的时候，就有报道称成年大鼠背柱损伤后体感丘脑出现了似乎是功能重组的现象，这一发现通过进一步实验得到了证实和扩展。为了证明这些发现不仅仅是对中枢损伤的反应，并更好地控制感觉丧失的程度，人们使用了外周神经损伤，这种损伤消除了上行感觉信息，同时使中枢通路保持完整。梅泽尼奇、卡斯及其同事利用外周神经横断来揭示灵长类动物体感皮层的明确重组。此外，这些研究人员还表明，这种可塑性至少经历两个阶段，一个是即时的，另一个是更持久的。这些发现得到了证实，并扩展到更广泛的皮层剥夺，进而扩展到丘脑和脑干。随后开始了一系列实验，以揭示允许这种可塑性的生理、形态和神经化学机制。最终，莫韦里及其同事进行了一系列实验，仔细追踪了灵长类动物体感皮层在周围神经损伤后的几个时间点上谷氨酸（AMPA和NMDA）和γ-氨基丁酸（GABAA和GABAB）受体复合物几个亚基的表达水平。这些受体亚基图谱实验表明，膜表达水平开始反映关键期发育早期的水平。这表明在长期感觉剥夺的条件下，成年细胞正在恢复到类似关键期的可塑性状态，即发育重演。在这里，我们概述了驱动这一现象的启发式方法。
