Abstract:
:Scientists have been fascinated by the human brain for centuries, yet knowledge of the cellular and molecular events that build the human brain during embryogenesis and of how abnormalities in this process lead to neurological disease remains very superficial. In particular, the lack of experimental models for a process that largely occurs during human in utero development, and is therefore poorly accessible for study, has hindered progress in mechanistic understanding. Advances in stem cell-derived models of human organogenesis, in the form of three-dimensional organoid cultures, and transformative new analytic technologies have opened new experimental pathways for investigation of aspects of development, evolution, and pathology of the human brain. Here, we consider the biology of brain organoids, compared and contrasted with the endogenous human brain, and highlight experimental strategies to use organoids to pioneer new understanding of human brain pathology.
journal_name
Annu Rev Neuroscijournal_title
Annual review of neuroscienceauthors
Velasco S,Paulsen B,Arlotta Pdoi
10.1146/annurev-neuro-070918-050154subject
Has Abstractpub_date
2020-07-08 00:00:00pages
375-389eissn
0147-006Xissn
1545-4126journal_volume
43pub_type
杂志文章abstract::Elucidating the roles of neuronal cell types for physiology and behavior is essential for understanding brain functions. Perturbation of neuron electrical activity can be used to probe the causal relationship between neuronal cell types and behavior. New genetically encoded neuron perturbation tools have been develope...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-071013-014048
更新日期:2014-01-01 00:00:00
abstract::Proteomic studies of the composition of mammalian synapses have revealed a high degree of complexity. The postsynaptic and presynaptic terminals are molecular systems with highly organized protein networks producing emergent physiological and behavioral properties. The major classes of synapse proteins and their respe...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-062111-150433
更新日期:2012-01-01 00:00:00
abstract::One goal of systems neuroscience is a structure-function model of nervous system organization that would allow mechanistic linking of mind, brain, and behavior. A necessary but not sufficient foundation is a connectome, a complete matrix of structural connections between the nodes of a nervous system. Connections betw...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-071714-033954
更新日期:2016-07-08 00:00:00
abstract::The genetic approach, based on the study of inherited forms of deafness, has proven to be particularly effective for deciphering the molecular mechanisms underlying the development of the peripheral auditory system, the cochlea and its afferent auditory neurons, and how this system extracts the physical parameters of ...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-070918-050428
更新日期:2019-07-08 00:00:00
abstract::The neocortex is found only in mammals, and the fossil record is silent on how this soft tissue evolved. Understanding neocortex evolution thus devolves to a search for candidate homologous neocortex traits in the extant nonmammalian amniotes. The difficulty is that homology is based on similarity, and the six-layered...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-071714-033911
更新日期:2015-07-08 00:00:00
abstract::Rhythmicity is a universal timing mechanism in the brain, and the rhythmogenic mechanisms are generally dynamic. This is illustrated for the neuronal control of breathing, a behavior that occurs as a one-, two-, or three-phase rhythm. Each breath is assembled stochastically, and increasing evidence suggests that each ...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-080317-061756
更新日期:2018-07-08 00:00:00
abstract::Neurons and synapses display a rich range of time-dependent processes. Which of these are critical to understanding specific integrative functions in the brain? Computational methods of various kinds are used to understand how systems of neurons interact to produce behavior. However, these models often assume that neu...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev.neuro.21.1.25
更新日期:1998-01-01 00:00:00
abstract::Ten years of remarkable progress in understanding the fundamental biochemistry of Alzheimer's disease have been followed by ten years of remarkable and increasing clinical insight into the natural progression of the disorder. The concept of a long, intermediary, prodromal phase between the first appearance of amyloid ...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-070815-014015
更新日期:2016-07-08 00:00:00
abstract::Neurons have their own systems for regulating RNA. Several multigene families encode RNA binding proteins (RNABPs) that are uniquely expressed in neurons, including the well-known neuron-specific markers ELAV and NeuN and the disease antigen NOVA. New technologies have emerged in recent years to assess the function of...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-062912-114322
更新日期:2013-07-08 00:00:00
abstract::According to embodied cognition theories, higher cognitive abilities depend on the reenactment of sensory and motor representations. In the first part of this review, we critically analyze the central claims of embodied theories and argue that the existing behavioral and neuroimaging data do not allow investigators to...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-071013-013950
更新日期:2014-01-01 00:00:00
abstract::Muscarinic signaling affects attention, action selection, learning, and memory through multiple signaling cascades, which act at different timescales and which alter ion channels in cell type-specific manners. The effects of muscarinic signaling differ between cortical layers and between brain areas. Muscarinic signal...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-062012-170433
更新日期:2013-07-08 00:00:00
abstract::Scientists in many different fields have been attracted to the study of habits because of the power habits have over behavior and because they invoke a dichotomy between the conscious, voluntary control over behavior, considered the essence of higher-order deliberative behavioral control, and lower-order behavioral co...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev.neuro.29.051605.112851
更新日期:2008-01-01 00:00:00
abstract::Binocular disparity provides the visual system with information concerning the three-dimensional layout of the environment. Recent physiological studies in the primary visual cortex provide a successful account of the mechanisms by which single neurons are able to signal disparity. This work also reveals that addition...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev.neuro.24.1.203
更新日期:2001-01-01 00:00:00
abstract::Trial-to-trial variability in the execution of movements and motor skills is ubiquitous and widely considered to be the unwanted consequence of a noisy nervous system. However, recent studies have suggested that motor variability may also be a feature of how sensorimotor systems operate and learn. This view, rooted in...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-072116-031548
更新日期:2017-07-25 00:00:00
abstract::Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that results primarily from the death of dopaminergic neurons in the substantia nigra. Although the etiology of PD is incompletely understood, the recent discovery of genes associated with rare monogenic forms of the disease, together with e...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev.neuro.28.061604.135718
更新日期:2005-01-01 00:00:00
abstract::Maturation of neuronal circuits requires selective elimination of synaptic connections. Although neuron-intrinsic mechanisms are important in this process, it is increasingly recognized that glial cells also play a critical role. Without proper functioning of these cells, the number, morphology, and function of synapt...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-070918-050306
更新日期:2019-07-08 00:00:00
abstract::The topographic assembly of neural circuits is dependent upon the generation of specific neuronal subtypes, each subtype displaying unique properties that direct the formation of selective connections with appropriate target cells. Studies of motor neuron development in the spinal cord have begun to elucidate the mole...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev.neuro.25.112701.142916
更新日期:2002-01-01 00:00:00
abstract::The mammalian central nervous system (CNS) requires the proper formation of exquisitely precise circuits to function correctly. These neuronal circuits are assembled during development by the formation of synaptic connections between thousands of differentiating neurons. Proper synapse formation during childhood provi...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev.neuro.29.051605.112830
更新日期:2007-01-01 00:00:00
abstract::Long-term depression (LTD) is a lasting decrease in synaptic effectiveness that follows some types of electrical stimulation in the hippocampus. Two broad types of LTD may be distinguished. Heterosynaptic LTD can occur at synapses that are inactive, normally during high-frequency stimulation of a converging synaptic i...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev.ne.19.030196.002253
更新日期:1996-01-01 00:00:00
abstract::The tragedy of epilepsy emerges from the combination of its high prevalence, impact upon sufferers and their families, and unpredictability. Childhood epilepsies are frequently severe, presenting in infancy with pharmaco-resistant seizures; are often accompanied by debilitating neuropsychiatric and systemic comorbidit...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-072116-031250
更新日期:2017-07-25 00:00:00
abstract::Human studies in the past three decades have provided us with an emerging understanding of how cortical and spinal networks collaborate to ensure the vast repertoire of human behaviors. Humans have direct cortical connections to spinal motoneurons, which bypass spinal interneurons and exert a direct (willful) muscle c...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-070815-013913
更新日期:2016-07-08 00:00:00
abstract::Why the cerebral cortex folds in some mammals but not in others has long fascinated and mystified neurobiologists. Over the past century-especially the past decade-researchers have used theory and experiment to support different folding mechanisms such as tissue buckling from mechanical stress, axon tethering, localiz...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-071714-034128
更新日期:2015-07-08 00:00:00
abstract::Cortical interneurons display striking differences in shape, physiology, and other attributes, challenging us to appropriately classify them. We previously suggested that interneuron types should be defined by their role in cortical processing. Here, we revisit the question of how to codify their diversity based upon ...
journal_title:Annual review of neuroscience
pub_type: 杂志文章
doi:10.1146/annurev-neuro-070918-050421
更新日期:2020-07-08 00:00:00
abstract::Classical neurotransmitters are synthesized in the cytoplasm, so they require transport into secretory vesicles for regulated exocytotic release. Previous work has identified distinct vesicular transport activities for the different classical transmitters, and all depend on the H+-electrochemical gradient across the v...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev.neuro.20.1.125
更新日期:1997-01-01 00:00:00
abstract::Parkinson's disease (PD) is a common neurodegenerative disease, yet the underlying causative molecular mechanisms are ill defined. Numerous observations based on drug studies and mutations in genes that cause PD point to a complex set of rather subtle mitochondrial defects that may be causative. Indeed, intensive inve...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev-neuro-071013-014317
更新日期:2014-01-01 00:00:00
abstract::A category of stimuli of great importance for primates, humans in particular, is that formed by actions done by other individuals. If we want to survive, we must understand the actions of others. Furthermore, without action understanding, social organization is impossible. In the case of humans, there is another facul...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev.neuro.27.070203.144230
更新日期:2004-01-01 00:00:00
abstract::The defining neuropathological characteristics of Alzheimer's disease are abundant filamentous tau lesions and deposits of fibrillar amyloid beta peptides. Prominent filamentous tau inclusions and brain degeneration in the absence of beta-amyloid deposits are also hallmarks of neurodegenerative tauopathies exemplified...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev.neuro.24.1.1121
更新日期:2001-01-01 00:00:00
abstract::Extensive electrophysiological experiments on Aplysia neurons have resulted in an understanding of simple behaviors in terms of the activities of a single identified neurons. Beginning with the work of Kupfermann & Kandel, neuropeptides in Aplysia have become increasingly implicated as chemical agents that control or ...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev.ne.08.030185.002243
更新日期:1985-01-01 00:00:00
abstract::Immunotherapeutic strategies to combat neurodegenerative disorders have galvanized the scientific community since the first dramatic successes in mouse models recreating aspects of Alzheimer disease (AD) were reported. However, initial human trials of active amyloid-beta (Abeta) vaccination were halted early because o...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev.neuro.31.060407.125529
更新日期:2008-01-01 00:00:00
abstract::The generation of distinct classes of neurons at defined positions within the developing vertebrate nervous system depends on inductive signals provided by local cell groups that act as organizing centers. Genetic and embryological studies have begun to elucidate the processes that control the pattern and identity of ...
journal_title:Annual review of neuroscience
pub_type: 杂志文章,评审
doi:10.1146/annurev.neuro.22.1.261
更新日期:1999-01-01 00:00:00