Neuroscience
-
Performance of supercomputers has been steadily and exponentially increasing for the past 20 years, and is expected to increase further. This unprecedented computational power enables us to build and simulate large-scale neural network models composed of tens of billions of neurons and tens of trillions of synapses with detailed anatomical connections and realistic physiological parameters. Such "human-scale" brain simulation could be considered a milestone in computational neuroscience and even in general neuroscience. ⋯ Then, we direct our attention to the cerebellum, with a review of more simulation studies specific to that region. Furthermore, we present recent simulation results of a human-scale cerebellar network model composed of 86 billion neurons on the Japanese flagship supercomputer K (now retired). Finally, we discuss the necessity and importance of human-scale brain simulation, and suggest future directions of such large-scale brain simulation research.
-
The cerebellum is thought to have a variety of functions because it developed with the evolution of the cerebrum and connects with different areas in the frontoparietal cortices. Like neurons in the cerebral cortex, those in the cerebellum also exhibit strong activity during planning in addition to the execution of movements. However, their specific roles remain elusive. ⋯ During a recently developed synchronized eye movement task, cerebellar nuclear neurons exhibited periodic preparatory activity for predictive synchronization. In all cases, the cerebellum generated preparatory activity lasting for several hundred milliseconds. These signals may regulate neuronal activity in the cerebral cortex that adjusts movement timing and predicts the timing of rhythmic events.
-
The cerebellum forms regular neural network structures consisting of a few major types of neurons, such as Purkinje cells, granule cells, and molecular layer interneurons, and receives two major inputs from climbing fibers and mossy fibers. Its regular structures consist of three well-defined layers, with each type of neuron designated to a specific location and forming specific synaptic connections. During the first few weeks of postnatal development in rodents, the cerebellum goes through dynamic changes via proliferation, migration, differentiation, synaptogenesis, and maturation, to create such a network structure. ⋯ Therefore, it is reasonable that extracellular signaling via synaptic transmission, secreted molecules, and cell adhesion molecules, plays important roles in cerebellar network development. Although it is not yet clear as to how overall cerebellar development is orchestrated, there is indeed accumulating lines of evidence that extracellular signaling acts toward the development of individual elements in the cerebellar networks. In this article, we introduce what we have learned from many studies regarding the extracellular signaling required for cerebellar network development, including our recent study suggesting the importance of unbiased synaptic inputs from parallel fibers.
-
Cerebellar development has a remarkably protracted morphogenetic timeline that is coordinated by multiple cell types. Here, we discuss the intriguing cellular consequences of interactions between inhibitory Purkinje cells and excitatory granule cells during embryonic and postnatal development. Purkinje cells are central to all cerebellar circuits, they are the first cerebellar cortical neurons to be born, and based on their cellular and molecular signaling, they are considered the master regulators of cerebellar development. ⋯ They provide a combination of mechanical, molecular and activity-based cues that shape the maturation of Purkinje cell structure, connectivity and function. We propose that the wiring of Purkinje cells for function falls into two developmental phases: an initial phase that is guided by intrinsic mechanisms and a later phase that is guided by dynamically-acting cues, some of which are provided by granule cells. In this review, we highlight the mechanisms that granule cells use to help establish the unique properties of Purkinje cell firing.
-
This article is dedicated to the memory of Masao Ito. Masao Ito made numerous important contributions revealing the function of the cerebellum in motor control. His pioneering contributions to cerebellar physiology began with his discovery of inhibition and disinhibition of target neurons by cerebellar Purkinje cells, and his discovery of the presence of long-term depression in parallel fiber-Purkinje cell synapses. ⋯ These discoveries became the basis for his ideas regarding the flocculus hypothesis, the adaptive motor control system, and motor learning by the cerebellum, inspiring many new experiments to test his hypotheses. This article will trace the achievements of Ito and colleagues in analyzing the neural circuits of the input-output organization of the cerebellar cortex and nuclei, particularly with respect to motor control. The article will discuss some of the important issues that have been solved and also those that remain to be solved for our understanding of motor control by the cerebellum.