Deep learning is a form of machine learning that enables computers to learn from experience and understand the world in terms of a hierarchy of concepts. Because the computer gathers knowledge from experience, there is no need for a human computer operator to formally specify all the knowledge that the computer needs. The hierarchy of concepts allows the computer to learn complicated concepts by building them out of simpler ones; a graph of these hierarchies would be many layers deep. This book introduces a broad range of topics in deep learning. The text offers mathematical and conceptual background, covering relevant concepts in linear algebra, probability theory and information theory, numerical computation, and machine learning. It describes deep learning techniques used by practitioners in industry, including deep feedforward networks, regularization, optimization algorithms, convolutional networks, sequence modeling, and practical methodology; and it surveys such applications as natural language processing, speech recognition, computer vision, online recommendation systems, bioinformatics, and videogames. Finally, the book offers research perspectives, covering such theoretical topics as linear factor models, autoencoders, representation learning, structured probabilistic models, Monte Carlo methods, the partition function, approximate inference, and deep generative models. Deep Learning can be used by undergraduate or graduate students planning careers in either industry or research, and by software engineers who want to begin using deep learning in their products or platforms. A website offers supplementary material for both readers and instructors.

Deep Learning

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The self-organized map, an architecture suggested for artificial neural networks, is explained by presenting simulation experiments and practical applications. The self-organizing map has the property of effectively creating spatially organized internal representations of various features of input signals and their abstractions. One result of this is that the self-organization process can discover semantic relationships in sentences. Brain maps, semantic maps, and early work on competitive learning are reviewed. The self-organizing map algorithm (an algorithm which order responses spatially) is reviewed, focusing on best matching cell selection and adaptation of the weight vectors. Suggestions for applying the self-organizing map algorithm, demonstrations of the ordering process, and an example of hierarchical clustering of data are presented. Fine tuning the map by learning vector quantization is addressed. The use of self-organized maps in practical speech recognition and a simulation experiment on semantic mapping are discussed. >

The self-organizing map

In recent years, many new cortical areas have been identified in the macaque monkey. The number of identified connections between areas has increased even more dramatically. We report here on (1) a summary of the layout of cortical areas associated with vision and with other modalities, (2) a computerized database for storing and representing large amounts of information on connectivity patterns, and (3) the application of these data to the analysis of hierarchical organization of the cerebral cortex. Our analysis concentrates on the visual system, which includes 25 neocortical areas that are predominantly or exclusively visual in function, plus an additional 7 areas that we regard as visual-association areas on the basis of their extensive visual inputs. A total of 305 connections among these 32 visual and visual-association areas have been reported. This represents 31% of the possible number of pathways if each area were connected with all others. The actual degree of connectivity is likely to be closer to 40%. The great majority of pathways involve reciprocal connections between areas. There are also extensive connections with cortical areas outside the visual system proper, including the somatosensory cortex, as well as neocortical, transitional, and archicortical regions in the temporal and frontal lobes. In the somatosensory/motor system, there are 62 identified pathways linking 13 cortical areas, suggesting an overall connectivity of about 40%. Based on the laminar patterns of connections between areas, we propose a hierarchy of visual areas and of somatosensory/motor areas that is more comprehensive than those suggested in other recent studies. The current version of the visual hierarchy includes 10 levels of cortical processing. Altogether, it contains 14 levels if one includes the retina and lateral geniculate nucleus at the bottom as well as the entorhinal cortex and hippocampus at the top. Within this hierarchy, there are multiple, intertwined processing streams, which, at a low level, are related to the compartmental organization of areas V1 and V2 and, at a high level, are related to the distinction between processing centers in the temporal and parietal lobes. However, there are some pathways and relationships (about 10% of the total) whose descriptions do not fit cleanly into this hierarchical scheme for one reason or another. In most instances, though, it is unclear whether these represent genuine exceptions to a strict hierarchy rather than inaccuracies or uncertainities in the reported assignment.

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Distributed Hierarchical Processing in the Primate Cerebral Cortex

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.

/pdf/astrocytes-biology-and-pathology-2hq13zf0bo.pdf

Astrocytes: biology and pathology

The development of highly interconnected circuits in the brain relies on patterns of neural activity. These patterns produce a cascade of events that refine initially imprecise connectivity into precise circuits. The presence of neural activity is particularly important during well-defined critical periods in early life.


Keywords:

visual system;
synapse;
retinal axons;
LTP;
critical period

Neural Activity and the Development of Brain Circuits

Dynamics of neuronal sensitivity in primate V1 underlying local feature discrimination

Very early in the development of neural connections in the brain, axons find their targets without the aid of neural activity. In subsequent stages of development, however, neural activity plays an important role. The visual pathway has provided important clues to the role of activity in brain development. The development of the precise point-to-point connections that underlie a functionally normal visual system requires patterned neural activity that in some cases is generated by the nervous system itself. Thereafter, neural activity generated by visual stimuli is required for the development and maintenance of precise connectivity. Lastly, neural activity must lead to long-term changes that mediate visual learning and memory. A good deal of evidence suggests that the mechanisms involved in the activity-dependent development of neural connections are similar to those underlying long-term changes in synaptic strength in the adult brain.

http://psychology.uwo.ca/undergraduate/psych347g/hohnke_99.pdf

Development of the visual pathways: Effects of neural activity

Intracellular recordings were used to examine the action potential firing modes of cells in the ferret lateral geniculate nucleus (LGN) in vitro. We compared the effects of altered membrane voltage on patterns of action potential trains evoked by direct current injection and by retinal afferent (synaptic) stimulation. The results confirm that LGN cells in the ferret can fire action potentials in the “burst” and “tonic” modes that have been described previously for other species. At depolarized membrane potentials, LGN neurons respond to sustained depolarization with short-latency trains of action potentials whose frequency is directly proportional to the amount of current injected. At hyperpolarized membrane potentials, LGN cells enter burst mode, in which depolarizing inputs are differentiated into brief high-frequency discharges whose latency varies with membrane potential. We also observed a “mixed” mode, in which LGN cell responses to synaptic or injected currents within a narrow range of membrane potentials reflect aspects of both burst and tonic firing simultaneously. Thus a striking consequence of the interplay among voltage-dependent membrane conductances in thalamic cells is wide variability in length, duration, and latency of spike discharges elicited by identical stimuli. These results also suggest that the concept that LGN cells display only two active response modes must be expanded to include varying amounts of delay and the possibility of mixed discharges.

Spike trains and signaling modes of neurons in the ferret lateral geniculate nucleus

Human cerebral organoids are unique in their development of progenitor-rich zones akin to ventricular zones from which neuronal progenitors differentiate and migrate radially. Analyses of cerebral organoids thus far have been performed in sectioned tissue or in superficial layers due to their high scattering properties. Here, we demonstrate label-free three-photon imaging of whole, uncleared intact organoids (∼2 mm depth) to assess early events of early human brain development. Optimizing a custom-made three-photon microscope to image intact cerebral organoids generated from Rett Syndrome patients, we show defects in the ventricular zone volumetric structure of mutant organoids compared to isogenic control organoids. Long-term imaging live organoids reveals that shorter migration distances and slower migration speeds of mutant radially migrating neurons are associated with more tortuous trajectories. Our label-free imaging system constitutes a particularly useful platform for tracking normal and abnormal development in individual organoids, as well as for screening therapeutic molecules via intact organoid imaging.

Mriganka Sur

Papers

Neural Activity and the Development of Brain Circuits

Dynamics of neuronal sensitivity in primate V1 underlying local feature discrimination

Development of the visual pathways: Effects of neural activity

Spike trains and signaling modes of neurons in the ferret lateral geniculate nucleus

Label-free three-photon imaging of intact human cerebral organoids for tracking early events in brain development and deficits in Rett syndrome