John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA 02138.
Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital, Boston, MA 02114.
Proc Natl Acad Sci U S A. 2024 Oct 15;121(42):e2411459121. doi: 10.1073/pnas.2411459121. Epub 2024 Oct 7.
The cerebellum is critical for sensorimotor learning. The specific contribution that it makes, however, remains unclear. Inspired by the classic finding that for declarative memories, medial temporal lobe (MTL) structures provide a gateway to the formation of long-term memory but are not required for short-term memory, we hypothesized that for sensorimotor memories, the cerebellum may play an analogous role. Here, we studied the sensorimotor learning of individuals with severe ataxia from cerebellar degeneration. We dissected the memories they formed during sensorimotor learning into a short-term temporally-volatile component, that decays rapidly with a time constant of just 15 to 20 s and thus cannot lead to long-term retention, and a longer-term temporally-persistent component that is stable for 60 s or more and leads to long-term retention. Remarkably, we find that these individuals display dramatically reduced levels of temporally-persistent sensorimotor memory, despite spared and even elevated levels of temporally-volatile sensorimotor memory. In particular, we find both impairment that systematically worsens with memory window duration over shorter memory windows (<12 s) and near-complete impairment of memory maintenance over longer memory windows (>25 s). This dissociation uncovers a unique role for the cerebellum as a gateway for the formation of long-term but not short-term sensorimotor memories, mirroring the role of the MTL for declarative memories. It thus reveals the existence of distinct neural substrates for short-term and long-term sensorimotor memory, and it explains both the trial-to-trial differences identified in this study and long-standing study-to-study differences in the effects of cerebellar damage on sensorimotor learning ability.
小脑对于感觉运动学习至关重要。然而,它具体的贡献仍不清楚。受经典发现的启发,即对于陈述性记忆,内侧颞叶(MTL)结构为长期记忆的形成提供了一个入口,但对于短期记忆来说并不是必需的,我们假设对于感觉运动记忆,小脑可能起到类似的作用。在这里,我们研究了来自小脑退化的严重共济失调个体的感觉运动学习。我们将他们在感觉运动学习过程中形成的记忆分解为短期的、暂态易变的成分,这种成分会迅速衰减,其时间常数仅为 15 到 20 秒,因此不能导致长期保留,以及一个更长时间的、暂态持久的成分,它可以稳定 60 秒或更长时间,并导致长期保留。值得注意的是,我们发现尽管这些个体的暂态感觉运动记忆水平保持不变,甚至升高,但他们的暂态持久感觉运动记忆水平却显著降低。具体来说,我们发现,在较短的记忆窗口(<12 秒)中,记忆窗口持续时间系统地恶化,以及在较长的记忆窗口(>25 秒)中几乎完全丧失记忆维持能力,都会导致这种损伤。这种分离揭示了小脑作为长期但不是短期感觉运动记忆形成的入口的独特作用,反映了 MTL 对陈述性记忆的作用。因此,它揭示了短期和长期感觉运动记忆的不同神经基础的存在,并解释了本研究中确定的以及长期以来小脑损伤对感觉运动学习能力影响的研究之间的研究差异的存在。